X-34130094-C-T

Variant names:

• chrX-34130094-C-T
• rs1922404143
• NM_203408.4:c.2185G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_203408.4(FAM47A):​c.2185G>A​(p.Val729Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,097,059 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: FAM47A NM_203408.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.275

Genes affected

FAM47A (HGNC:29962): (family with sequence similarity 47 member A)

ENSG00000233928 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.024528742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47A	NM_203408.4	c.2185G>A	p.Val729Ile	missense_variant	Exon 1 of 1	ENST00000346193.5	NP_981953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM47A	ENST00000346193.5	c.2185G>A	p.Val729Ile	missense_variant	Exon 1 of 1	6	NM_203408.4	ENSP00000345029.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1097059 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 362469

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 08, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.043
DANN	Benign	0.14
DEOGEN2	Benign	0.0027	T;.
FATHMM_MKL	Benign	0.00010	N
LIST_S2	Benign	0.12	T;T
M_CAP	Benign	0.00074	T
MetaRNN	Benign	0.025	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.8	N;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.53	N;.
REVEL	Benign	0.035
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.18	B;.
Vest4		0.052
MutPred		0.15		Gain of disorder (P = 0.147);.;
MVP		0.068
MPC		0.19
ClinPred		0.038	T
GERP RS		-2.3
Varity_R		0.022
gMVP		0.013

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

Other links and lift over

dbSNP: rs1922404143; hg19: chrX-34148211; COSMIC: COSV60494022;