4-88750589-T-A

Position:

• chr4-88750589-T-A

Variant summary

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

The NM_014883.4(FAM13A):​c.1775A>T​(p.Asp592Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM13A NM_014883.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79

Genes affected

FAM13A (HGNC:19367): (family with sequence similarity 13 member A) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. Implicated in chronic obstructive pulmonary disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM13A	NM_014883.4	c.1775A>T	p.Asp592Val	missense_variant	15/24	ENST00000264344.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM13A	ENST00000264344.10	c.1775A>T	p.Asp592Val	missense_variant	15/24	5	NM_014883.4	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.1775A>T (p.D592V) alteration is located in exon 15 (coding exon 15) of the FAM13A gene. This alteration results from a A to T substitution at nucleotide position 1775, causing the aspartic acid (D) at amino acid position 592 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	0.15
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	.;T;.;T;.;.
Eigen	Benign	0.16
Eigen_PC	Benign	0.060
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.9	.;L;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.3	D;D;D;D;D;D
REVEL	Benign	0.18
Sift	Benign	0.16	T;T;T;T;T;T
Sift4G	Uncertain	0.032	D;D;D;D;D;D
Polyphen		0.98	D;D;D;D;D;D
Vest4		0.49
MutPred		0.22		.;Gain of glycosylation at S589 (P = 0.0073);.;.;.;.;
MVP		0.68
MPC		0.76
ClinPred		0.97	D
GERP RS		4.3
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.29
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr4-89671740;