NM_014883.4:c.2783A>T

Variant names:

• chr4-88732062-T-A
• NM_014883.4:c.2783A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014883.4(FAM13A):​c.2783A>T​(p.Asp928Val) variant causes a missense change. 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: 32)
• Consequence: FAM13A NM_014883.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.12

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41156444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM13A	NM_014883.4	c.2783A>T	p.Asp928Val	missense_variant	Exon 22 of 24	ENST00000264344.10	NP_055698.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM13A	ENST00000264344.10	c.2783A>T	p.Asp928Val	missense_variant	Exon 22 of 24	5	NM_014883.4	ENSP00000264344.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2783A>T (p.D928V) alteration is located in exon 22 (coding exon 22) of the FAM13A gene. This alteration results from a A to T substitution at nucleotide position 2783, causing the aspartic acid (D) at amino acid position 928 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	0.23
BayesDel_addAF	Benign	-0.0073	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	.;T;.;T;.;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.41	T;T;T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.7	.;L;.;.;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.1	D;D;D;D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D;D;D;D;D;D
Sift4G	Benign	0.080	T;D;D;D;D;D
Polyphen		0.79	P;P;P;D;P;P
Vest4		0.46
MutPred		0.34		.;Loss of disorder (P = 0.004);.;.;.;.;
MVP		0.66
MPC		0.76
ClinPred		0.99	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.34

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: chr4-89653213;