Genetic Variant TEKTIP1:p.Gly60Ser (chr19-3543329-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001135580.2(TEKTIP1):c.178G>A(p.Gly60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000671 in 1,549,292 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000059 ( 1 hom. )

Consequence

TEKTIP1
NM_001135580.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.704

Publications

0 publications found

Variant links:

Genes affected

TEKTIP1 (HGNC:34496): (tektin bundle interacting protein 1)

TEKTIP1 links:

MFSD12 (HGNC:28299): (major facilitator superfamily domain containing 12) Enables cysteine transmembrane transporter activity. Involved in cysteine transmembrane transport; pigment metabolic process involved in pigmentation; and regulation of melanin biosynthetic process. Located in lysosome and melanosome. Part of late endosome. [provided by Alliance of Genome Resources, Apr 2022]

MFSD12 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023843497).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135580.2. 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
	TEKTIP1	NM_001135580.2	MANE Select	c.178G>A	p.Gly60Ser	missense	Exon 2 of 4	NP_001129052.1	A6NCJ1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TEKTIP1	ENST00000329493.6	TSL:2 MANE Select	c.178G>A	p.Gly60Ser	missense	Exon 2 of 4	ENSP00000327950.4	A6NCJ1
TEKTIP1	ENST00000681976.1		c.19G>A	p.Gly7Ser	missense	Exon 2 of 4	ENSP00000507755.1	A0A804HK34
MFSD12	ENST00000398558.8	TSL:2	c.329-352C>T		intron	N/A	ENSP00000381566.4	A0A0A0MS91

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000658

AC:

AN:

151964

AF XY:

0.0000616

show subpopulations

Gnomad AFR exome

AF:

0.000774

Gnomad AMR exome

AF:

0.0000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000342

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000587

AC:

AN:

1397136

Hom.:

Cov.:

AF XY:

0.0000580

AC XY:

AN XY:

689116

show subpopulations

African (AFR)

AF:

0.000412

AC:

AN:

31568

American (AMR)

AF:

0.0000840

AC:

AN:

35698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25172

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35736

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47798

Middle Eastern (MID)

AF:

0.000193

AC:

AN:

5178

European-Non Finnish (NFE)

AF:

0.0000556

AC:

AN:

1078878

Other (OTH)

AF:

0.0000518

AC:

AN:

57918

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000145

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.000435

AC:

AN:

41416

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

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:

0.000129

Hom.:

Bravo

AF:

0.000178

ExAC

AF:

0.000151

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.73

M_CAP

Benign

0.028

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.3

PhyloP100

0.70

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.061

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.70

Vest4

0.24

MutPred

0.39

Gain of helix (P = 0.0425)

MVP

0.12

ClinPred

0.20

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.56

gMVP

0.27

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

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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