Variant X-8795299-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_174951.3(FAM9A):c.610G>A(p.Ala204Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,198,906 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 39 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.00013 ( 0 hom. 38 hem. )

Consequence

FAM9A
NM_174951.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.214

Variant links:

Genes affected

FAM9A (HGNC:18403): (family with sequence similarity 9 member A) This gene is a member of a gene family which arose through duplication on the X chromosome. The encoded protein may be a nuclear protein that is localized to the nucleolus, and has some similarity to a synaptonemal complex protein. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Aug 2011]

FAM9A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.071309626).

BS2

High Hemizygotes in GnomAdExome4 at 38 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM9A	NM_174951.3 linkuse as main transcript	c.610G>A	p.Ala204Thr	missense_variant	7/10	ENST00000381003.7
FAM9A	NM_001171186.1 linkuse as main transcript	c.610G>A	p.Ala204Thr	missense_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM9A	ENST00000381003.7 linkuse as main transcript	c.610G>A	p.Ala204Thr	missense_variant	7/10	1	NM_174951.3	P1
FAM9A	ENST00000543214.1 linkuse as main transcript	c.610G>A	p.Ala204Thr	missense_variant	7/10	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0000727

AC:

AN:

109989

Hom.:

Cov.:

AF XY:

0.0000309

AC XY:

AN XY:

32345

show subpopulations

Gnomad AFR

AF:

0.0000332

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00426

Gnomad NFE

AF:

0.000114

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000118

AC:

AN:

168968

Hom.:

AF XY:

0.0000848

AC XY:

AN XY:

58964

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000244

Gnomad OTH exome

AF:

0.000472

GnomAD4 exome

AF:

0.000130

AC:

142

AN:

1088863

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

357075

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000373

Gnomad4 FIN exome

AF:

0.0000261

Gnomad4 NFE exome

AF:

0.000154

Gnomad4 OTH exome

AF:

0.0000877

GnomAD4 genome

AF:

0.0000727

AC:

AN:

110043

Hom.:

Cov.:

AF XY:

0.0000309

AC XY:

AN XY:

32405

show subpopulations

Gnomad4 AFR

AF:

0.0000331

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000114

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.0000839

AC:

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

May 11, 2022

The c.610G>A (p.A204T) alteration is located in exon 7 (coding exon 6) of the FAM9A gene. This alteration results from a G to A substitution at nucleotide position 610, causing the alanine (A) at amino acid position 204 to be replaced by a threonine (T). 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

0.27

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.1

DANN

Benign

0.89

DEOGEN2

Benign

0.0081

T;T

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.27

T;.

M_CAP

Benign

0.00063

MetaRNN

Benign

0.071

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-0.44

N;N

REVEL

Benign

0.044

Sift

Benign

0.22

T;T

Sift4G

Uncertain

0.012

D;D

Polyphen

0.85

P;P

Vest4

0.16

MVP

0.50

MPC

0.052

ClinPred

0.026

GERP RS

0.15

Varity_R

0.089

gMVP

0.021

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