X-34130018-A-G

Variant names:

• chrX-34130018-A-G
• rs1418593317
• NM_203408.4:c.2261T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203408.4(FAM47A):​c.2261T>C​(p.Ile754Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: FAM47A NM_203408.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18

Genes affected

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

ENSG00000233928 (HGNC:):

ACMG classification

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=0.19357246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47A	NM_203408.4	c.2261T>C	p.Ile754Thr	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.2261T>C	p.Ile754Thr	missense_variant	Exon 1 of 1	6	NM_203408.4	ENSP00000345029.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2261T>C (p.I754T) alteration is located in exon 1 (coding exon 1) of the FAM47A gene. This alteration results from a T to C substitution at nucleotide position 2261, causing the isoleucine (I) at amino acid position 754 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	Pathogenic	0.90
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.11	T;.
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.00092	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-4.0	D;.
REVEL	Benign	0.054
Sift	Uncertain	0.0040	D;.
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.24	B;.
Vest4		0.40
MutPred		0.56		Loss of helix (P = 0.0167);.;
MVP		0.043
MPC		0.27
ClinPred		0.27	T
GERP RS		1.1
Varity_R		0.23
gMVP		0.086

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: rs1418593317; hg19: chrX-34148135;