Variant X-13040783-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_174901.6(FAM9C):c.304G>A(p.Val102Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000152 in 1,185,242 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V102A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000044 ( 0 hom., 3 hem., cov: 24)

Exomes 𝑓: 0.000012 ( 0 hom. 4 hem. )

Consequence

FAM9C
NM_174901.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.276

Variant links:

Genes affected

FAM9C (HGNC:18405): (family with sequence similarity 9 member C) This gene is a member of a gene family which arose through duplication on the X chromosome. The encoded protein may be localized to the nucleus as the protein contains several nuclear localization signals, and has similarity to a synaptonemal complex protein. [provided by RefSeq, Aug 2011]

FAM9C 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=0.069827884).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FAM9C	NM_174901.6 linkuse as main transcript	c.304G>A	p.Val102Ile	missense_variant	5/8	ENST00000380625.8
FAM9C	XM_024452348.2 linkuse as main transcript	c.616G>A	p.Val206Ile	missense_variant	5/7
FAM9C	XM_005274460.4 linkuse as main transcript	c.304G>A	p.Val102Ile	missense_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM9C	ENST00000380625.8 linkuse as main transcript	c.304G>A	p.Val102Ile	missense_variant	5/8	1	NM_174901.6	P1

Frequencies

GnomAD3 genomes

AF:

0.0000444

AC:

AN:

112592

Hom.:

Cov.:

AF XY:

0.0000863

AC XY:

AN XY:

34754

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000469

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:

0.00

GnomAD4 exome

AF:

0.0000121

AC:

AN:

1072650

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

345118

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000130

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000408

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.0000887

GnomAD4 genome

AF:

0.0000444

AC:

AN:

112592

Hom.:

Cov.:

AF XY:

0.0000863

AC XY:

AN XY:

34754

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000469

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000155

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 18, 2022

The c.304G>A (p.V102I) alteration is located in exon 5 (coding exon 4) of the FAM9C gene. This alteration results from a G to A substitution at nucleotide position 304, causing the valine (V) at amino acid position 102 to be replaced by an isoleucine (I). 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

0.081

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.16

DANN

Benign

0.058

DEOGEN2

Benign

0.028

T;T

FATHMM_MKL

Benign

0.036

M_CAP

Benign

0.0021

MetaRNN

Benign

0.070

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.90

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.50

N;N

REVEL

Benign

0.048

Sift

Benign

0.44

T;T

Sift4G

Benign

0.69

T;T

Polyphen

0.0

B;B

Vest4

0.17

MutPred

0.34

Gain of methylation at K100 (P = 0.1009);Gain of methylation at K100 (P = 0.1009);

MVP

0.30

MPC

0.012

ClinPred

0.030

GERP RS

0.59

Varity_R

0.068

gMVP

0.016

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