chr4-1641465-C-A

Variant names:

• chr4-1641465-C-A
• NM_001174070.3:c.1025G>T

Variant summary

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

The NM_001174070.3(FAM53A):​c.1025G>T​(p.Gly342Val) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM53A NM_001174070.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.825

Genes affected

FAM53A (HGNC:31860): (family with sequence similarity 53 member A) Predicted to be involved in protein import into nucleus. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.049172044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM53A	NM_001174070.3	c.1025G>T	p.Gly342Val	missense_variant	Exon 5 of 5	ENST00000308132.11	NP_001167541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM53A	ENST00000308132.11	c.1025G>T	p.Gly342Val	missense_variant	Exon 5 of 5	2	NM_001174070.3	ENSP00000310057.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1025G>T (p.G342V) alteration is located in exon 5 (coding exon 4) of the FAM53A gene. This alteration results from a G to T substitution at nucleotide position 1025, causing the glycine (G) at amino acid position 342 to be replaced by a valine (V). 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	0.079
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.55
DANN	Benign	0.25
DEOGEN2	Benign	0.0038	T;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.44	T;.;.
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.049	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L;L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.21	N;N;N
REVEL	Benign	0.028
Sift	Benign	0.36	T;T;T
Sift4G	Benign	0.63	T;T;T
Polyphen		0.10	B;B;B
Vest4		0.040
MutPred		0.17		Gain of glycosylation at T345 (P = 0.0122);Gain of glycosylation at T345 (P = 0.0122);Gain of glycosylation at T345 (P = 0.0122);
MVP		0.12
MPC		0.46
ClinPred		0.12	T
GERP RS		-2.4
Varity_R		0.041
gMVP		0.040

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.

Other links and lift over

hg19: chr4-1643192;