Variant X-13040782-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_174901.6(FAM9C):c.305T>C(p.Val102Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000932 in 1,073,019 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 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. V102I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.3e-7 ( 0 hom. 1 hem. )

Consequence

FAM9C
NM_174901.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12166339).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FAM9C	NM_174901.6 linkuse as main transcript	c.305T>C	p.Val102Ala	missense_variant	5/8	ENST00000380625.8
FAM9C	XM_024452348.2 linkuse as main transcript	c.617T>C	p.Val206Ala	missense_variant	5/7
FAM9C	XM_005274460.4 linkuse as main transcript	c.305T>C	p.Val102Ala	missense_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM9C	ENST00000380625.8 linkuse as main transcript	c.305T>C	p.Val102Ala	missense_variant	5/8	1	NM_174901.6	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.32e-7

AC:

AN:

1073019

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

345337

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000337

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 30, 2022

The c.305T>C (p.V102A) alteration is located in exon 5 (coding exon 4) of the FAM9C gene. This alteration results from a T to C substitution at nucleotide position 305, causing the valine (V) at amino acid position 102 to be replaced by an alanine (A). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.5

DANN

Benign

0.20

DEOGEN2

Benign

0.025

T;T

FATHMM_MKL

Benign

0.073

M_CAP

Benign

0.0015

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.69

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.64

N;N

REVEL

Benign

0.029

Sift

Benign

0.43

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.025

B;B

Vest4

0.42

MutPred

0.43

Loss of stability (P = 0.031);Loss of stability (P = 0.031);

MVP

0.52

MPC

0.013

ClinPred

0.032

GERP RS

0.15

Varity_R

0.052

gMVP

0.062

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over