4-88732054-G-T

Variant names:

• chr4-88732054-G-T
• rs140140106
• NM_014883.4:c.2791C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014883.4(FAM13A):​c.2791C>A​(p.Pro931Thr) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P931S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM13A NM_014883.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19758937).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014883.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM13A	NM_014883.4	MANE Select	c.2791C>A	p.Pro931Thr	missense	Exon 22 of 24	NP_055698.2	O94988-4
	FAM13A	NM_001015045.3		c.1813C>A	p.Pro605Thr	missense	Exon 16 of 18	NP_001015045.1	O94988-1
	FAM13A	NM_001265578.2		c.1771C>A	p.Pro591Thr	missense	Exon 15 of 17	NP_001252507.1	O94988-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM13A	ENST00000264344.10	TSL:5 MANE Select	c.2791C>A	p.Pro931Thr	missense	Exon 22 of 24	ENSP00000264344.5	O94988-4
	FAM13A	ENST00000503556.5	TSL:1	c.1771C>A	p.Pro591Thr	missense	Exon 15 of 17	ENSP00000427189.1	O94988-5
	FAM13A	ENST00000395002.6	TSL:1	c.1729C>A	p.Pro577Thr	missense	Exon 15 of 17	ENSP00000378450.2	O94988-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251228 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.048
Eigen_PC	Benign	0.079
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.8
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.10
Sift	Benign	0.16	T
Sift4G	Benign	0.57	T
Polyphen		0.21	B
Vest4		0.21
MutPred		0.12		Gain of glycosylation at S932 (P = 0.0575)
MVP		0.58
MPC		0.34
ClinPred		0.43	T
GERP RS		5.5
Varity_R		0.092
gMVP		0.28
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs140140106; hg19: chr4-89653205;