NM_014883.4:c.2791C>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014883.4(FAM13A):​c.2791C>T​(p.Pro931Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000279 in 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: FAM13A NM_014883.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15871033).

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>T	p.Pro931Ser	missense	Exon 22 of 24	NP_055698.2	O94988-4
	FAM13A	NM_001015045.3		c.1813C>T	p.Pro605Ser	missense	Exon 16 of 18	NP_001015045.1	O94988-1
	FAM13A	NM_001265578.2		c.1771C>T	p.Pro591Ser	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>T	p.Pro931Ser	missense	Exon 22 of 24	ENSP00000264344.5	O94988-4
	FAM13A	ENST00000503556.5	TSL:1	c.1771C>T	p.Pro591Ser	missense	Exon 15 of 17	ENSP00000427189.1	O94988-5
	FAM13A	ENST00000395002.6	TSL:1	c.1729C>T	p.Pro577Ser	missense	Exon 15 of 17	ENSP00000378450.2	O94988-3

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000179 AC: 45 AN: 251228 AF XY: 0.000214

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000308

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000291 AC: 425 AN: 1461636 Hom.: 0 Cov.: 30 AF XY: 0.000296 AC XY: 215 AN XY: 727116

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.000201 AC: 9 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000356 AC: 396 AN: 1111848

Other (OTH) AF: 0.000298 AC: 18 AN: 60388

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74452

African (AFR) AF: 0.000120 AC: 5 AN: 41556

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000324 Hom.: 1

Bravo AF: 0.000185

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000222 AC: 27

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.8
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.10
Sift	Benign	0.29	T
Sift4G	Benign	0.72	T
Polyphen		0.81	P
Vest4		0.18
MVP		0.56
MPC		0.31
ClinPred		0.042	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.066
gMVP		0.26
Mutation Taster		=88/12	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;