21-44574088-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_198687.2(KRTAP10-4):c.330C>T(p.Cys110Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000332 in 1,607,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 36)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

KRTAP10-4
NM_198687.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.21

Publications

0 publications found

Variant links:

Genes affected

KRTAP10-4 (HGNC:20521): (keratin associated protein 10-4) This is an intronless gene located in a cluster of related genes on the q arm of chromosome 21. The proteins encoded by these genes form disulfide bonds with cysteine residues in hair keratins, thereby contributing to the structure and stability of hair fibers. [provided by RefSeq, Apr 2014]

KRTAP10-4 links:

TSPEAR (HGNC:1268): (thrombospondin type laminin G domain and EAR repeats) This gene encodes a protein that contains a N-terminal thrombospondin-type laminin G domain and several tandem arranged epilepsy-associated repeats (EARs). A mutation in this gene is the cause of autosomal recessive deafness-98. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

TSPEAR Gene-Disease associations (from GenCC):

ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive nonsyndromic hearing loss 98
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

TSPEAR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 21-44574088-C-T is Benign according to our data. Variant chr21-44574088-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1695031.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.21 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198687.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTAP10-4	NM_198687.2	MANE Select	c.330C>T	p.Cys110Cys	synonymous	Exon 1 of 1	NP_941960.2	P60372
TSPEAR	NM_144991.3	MANE Select	c.83-6083G>A		intron	N/A	NP_659428.2
TSPEAR	NM_001272037.2		c.-122-6083G>A		intron	N/A	NP_001258966.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTAP10-4	ENST00000400374.4	TSL:6 MANE Select	c.330C>T	p.Cys110Cys	synonymous	Exon 1 of 1	ENSP00000383225.3	P60372
TSPEAR	ENST00000323084.9	TSL:1 MANE Select	c.83-6083G>A		intron	N/A	ENSP00000321987.4	Q8WU66-1
TSPEAR	ENST00000943283.1		c.83-6083G>A		intron	N/A	ENSP00000613342.1

Frequencies

GnomAD3 genomes

AF:

0.000673

AC:

101

AN:

150040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00166

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000728

Gnomad ASJ

AF:

0.000578

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000961

Gnomad MID

AF:

0.00993

Gnomad NFE

AF:

0.000222

Gnomad OTH

AF:

0.000976

GnomAD2 exomes

AF:

0.000330

AC:

AN:

248364

AF XY:

0.000363

show subpopulations

Gnomad AFR exome

AF:

0.00112

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.0000998

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000267

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.000297

AC:

433

AN:

1457212

Hom.:

Cov.:

175

AF XY:

0.000323

AC XY:

234

AN XY:

724960

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00130

AC:

AN:

33110

American (AMR)

AF:

0.000629

AC:

AN:

44530

Ashkenazi Jewish (ASJ)

AF:

0.000269

AC:

AN:

25978

East Asian (EAS)

AF:

0.00

AC:

AN:

39448

South Asian (SAS)

AF:

0.000499

AC:

AN:

86106

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53246

Middle Eastern (MID)

AF:

0.00979

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.000197

AC:

219

AN:

1109042

Other (OTH)

AF:

0.000600

AC:

AN:

60032

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.352

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000673

AC:

101

AN:

150148

Hom.:

Cov.:

AF XY:

0.000654

AC XY:

AN XY:

73360

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00165

AC:

AN:

40522

American (AMR)

AF:

0.000727

AC:

AN:

15132

Ashkenazi Jewish (ASJ)

AF:

0.000578

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5012

South Asian (SAS)

AF:

0.00

AC:

AN:

4760

European-Finnish (FIN)

AF:

0.0000961

AC:

AN:

10410

Middle Eastern (MID)

AF:

0.0106

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.000222

AC:

AN:

67590

Other (OTH)

AF:

0.000967

AC:

AN:

2068

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.365

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000240

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.60

(source)

DANN

Benign

0.74

PhyloP100

-3.2

PromoterAI

-0.039

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over