Genetic Variant TSGA10:p.Asp544Glu (chr2-99020465-A-C) – 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_025244.4(TSGA10):c.1632T>G(p.Asp544Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000416 in 1,611,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

TSGA10
NM_025244.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.546

Publications

0 publications found

Variant links:

Genes affected

TSGA10 (HGNC:14927): (testis specific 10) Predicted to enable structural molecule activity. Predicted to be involved in spermatogenesis. Predicted to act upstream of or within cell projection assembly. Predicted to be located in neuron projection; sperm fibrous sheath; and sperm principal piece. Implicated in spermatogenic failure 26. [provided by Alliance of Genome Resources, Apr 2022]

TSGA10 Gene-Disease associations (from GenCC):

spermatogenic failure 26
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

TSGA10 links:

Genome browser will be placed here

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=0.015719771).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025244.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSGA10	NM_025244.4	MANE Select	c.1632T>G	p.Asp544Glu	missense	Exon 18 of 21	NP_079520.1	A0A218MIY9
TSGA10	NM_001349012.1		c.1632T>G	p.Asp544Glu	missense	Exon 16 of 19	NP_001335941.1	A0A218MIY9
TSGA10	NM_182911.4		c.1632T>G	p.Asp544Glu	missense	Exon 17 of 20	NP_878915.2	A0A218MIY9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSGA10	ENST00000393483.8	TSL:1 MANE Select	c.1632T>G	p.Asp544Glu	missense	Exon 18 of 21	ENSP00000377123.3	Q9BZW7-1
TSGA10	ENST00000355053.8	TSL:1	c.1632T>G	p.Asp544Glu	missense	Exon 17 of 20	ENSP00000347161.4	Q9BZW7-1
TSGA10	ENST00000410001.5	TSL:1	c.1632T>G	p.Asp544Glu	missense	Exon 16 of 19	ENSP00000386956.1	Q9BZW7-1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000718

AC:

AN:

250560

AF XY:

0.0000443

show subpopulations

Gnomad AFR exome

AF:

0.000870

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000206

AC:

AN:

1459652

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726138

show subpopulations

African (AFR)

AF:

0.000628

AC:

AN:

33434

American (AMR)

AF:

0.000157

AC:

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39604

South Asian (SAS)

AF:

0.00

AC:

AN:

86136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110232

Other (OTH)

AF:

0.0000332

AC:

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

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:

0.000243

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.000821

AC:

AN:

41436

American (AMR)

AF:

0.000131

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.000479

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.000145

Hom.:

Bravo

AF:

0.000264

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

ClinVar submissions as Germline

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

0.083

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.020

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.72

M_CAP

Benign

0.0077

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.34

PhyloP100

0.55

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.78

REVEL

Benign

0.096

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.071

Vest4

0.12

MutPred

0.12

Gain of phosphorylation at S545 (P = 0.171)

MVP

0.13

MPC

0.12

ClinPred

0.021

GERP RS

3.0

Varity_R

0.040

gMVP

0.030

Mutation Taster

=94/6

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