NM_198690.3:c.72G>A

Variant names:

• chr21-44627243-G-A
• rs201201187
• NM_198690.3:c.72G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_198690.3(KRTAP10-9):​c.72G>A​(p.Glu24Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000732 in 1,612,732 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 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000076 (0 hom.)
• Consequence: KRTAP10-9 NM_198690.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.04
• Publications: 4 publications found

Genes affected

KRTAP10-9 (HGNC:22971): (keratin associated protein 10-9) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 21-44627243-G-A is Benign according to our data. Variant chr21-44627243-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2652772.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.05 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198690.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP10-9	NM_198690.3	MANE Select	c.72G>A	p.Glu24Glu	synonymous	Exon 1 of 1	NP_941963.2	P60411-1
	TSPEAR	NM_144991.3	MANE Select	c.83-59238C>T		intron	N/A	NP_659428.2
	TSPEAR	NM_001272037.2		c.-122-59238C>T		intron	N/A	NP_001258966.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP10-9	ENST00000397911.5	TSL:6 MANE Select	c.72G>A	p.Glu24Glu	synonymous	Exon 1 of 1	ENSP00000381009.3	P60411-1
	TSPEAR	ENST00000323084.9	TSL:1 MANE Select	c.83-59238C>T		intron	N/A	ENSP00000321987.4	Q8WU66-1
	KRTAP10-9	ENST00000484861.1	TSL:1	n.121G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152162 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000104 AC: 26 AN: 249598 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.0000760 AC: 111 AN: 1460452 Hom.: 0 Cov.: 31 AF XY: 0.0000991 AC XY: 72 AN XY: 726560

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.0000894 AC: 4 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86184

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53400

Middle Eastern (MID) AF: 0.00151 AC: 7 AN: 4650

European-Non Finnish (NFE) AF: 0.0000576 AC: 64 AN: 1111978

Other (OTH) AF: 0.000216 AC: 13 AN: 60266

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152280 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74444

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000604

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.8
DANN	Benign	0.87
PhyloP100		2.0
PromoterAI		0.018	Neutral
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs201201187; hg19: chr21-46047160; COSMIC: COSV59957849;