4-88749009-T-G

Variant names:

• chr4-88749009-T-G
• NM_014883.4:c.2104A>C

Variant summary

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

The NM_014883.4(FAM13A):​c.2104A>C​(p.Asn702His) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 7.93

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 rank	MANE	Protein	UniProt
FAM13A	NM_014883.4	c.2104A>C	p.Asn702His	missense_variant	Exon 17 of 24	ENST00000264344.10	NP_055698.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM13A	ENST00000264344.10	c.2104A>C	p.Asn702His	missense_variant	Exon 17 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

Jun 11, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2104A>C (p.N702H) alteration is located in exon 17 (coding exon 17) of the FAM13A gene. This alteration results from a A to C substitution at nucleotide position 2104, causing the asparagine (N) at amino acid position 702 to be replaced by a histidine (H). 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	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	.;T;.;T;.;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D
M_CAP	Uncertain	0.086	D
MetaRNN	Uncertain	0.73	D;D;D;D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.5	.;M;.;.;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-4.2	D;D;D;D;D;D
REVEL	Uncertain	0.40
Sift	Benign	0.036	D;D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D;D
Polyphen		1.0	D;D;D;D;D;D
Vest4		0.72
MutPred		0.19		.;Gain of glycosylation at S697 (P = 0.0138);.;.;.;.;
MVP		0.81
MPC		0.76
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.47
gMVP		0.33

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: chr4-89670160;