Variant chr1-32361784-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001167676.2(FAM229A):c.227C>T(p.Ala76Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00062 in 1,324,002 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00065 ( 4 hom. )

Consequence

FAM229A
NM_001167676.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.13

Variant links:

Genes affected

FAM229A (HGNC:44652): (family with sequence similarity 229 member A)

FAM229A links:

FAM229A (HGNC:):

FAM229A links:

TSSK3 (HGNC:15473): (testis specific serine kinase 3) This gene encodes a kinase expressed exclusively in the testis that is thought to play a role in either germ cell differentiation or mature sperm function. [provided by RefSeq, Jul 2008]

TSSK3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007926911).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM229A	NM_001167676.2 linkuse as main transcript	c.227C>T	p.Ala76Val	missense_variant	2/3	ENST00000432622.2	NP_001161148.1	H3BQW9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM229A	ENST00000432622.2 linkuse as main transcript	c.227C>T	p.Ala76Val	missense_variant	2/3	2	NM_001167676.2	ENSP00000455971.1		H3BQW9

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00143

AC:

AN:

1400

Hom.:

AF XY:

0.00133

AC XY:

AN XY:

754

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00376

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00172

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000645

AC:

756

AN:

1171740

Hom.:

Cov.:

AF XY:

0.000707

AC XY:

398

AN XY:

563090

show subpopulations

Gnomad4 AFR exome

AF:

0.0000427

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00356

Gnomad4 FIN exome

AF:

0.000252

Gnomad4 NFE exome

AF:

0.000585

Gnomad4 OTH exome

AF:

0.000395

GnomAD4 genome

AF:

0.000427

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00310

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.000355

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000185

AC:

Asia WGS

AF:

0.00116

AC:

AN:

3468

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 06, 2021

The c.227C>T (p.A76V) alteration is located in exon 2 (coding exon 2) of the FAM229A gene. This alteration results from a C to T substitution at nucleotide position 227, causing the alanine (A) at amino acid position 76 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.061

T;.

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.53

T;T

MetaRNN

Benign

0.0079

T;T

MutationAssessor

Benign

0.55

N;.

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.6

D;D

Sift

Benign

0.087

T;.

Sift4G

Benign

0.46

T;T

Vest4

0.076

MVP

0.25

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.16

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over