4-88747647-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014883.4(FAM13A):c.2366G>A(p.Arg789His) variant causes a missense change. The variant allele was found at a frequency of 0.000527 in 1,614,034 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00069 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (1 hom.)
• Consequence: FAM13A NM_014883.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.89

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008941919).
• BP6: Variant 4-88747647-C-T is Benign according to our data. Variant chr4-88747647-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 714040.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM13A	NM_014883.4	c.2366G>A	p.Arg789His	missense_variant	18/24	ENST00000264344.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM13A	ENST00000264344.10	c.2366G>A	p.Arg789His	missense_variant	18/24	5	NM_014883.4	P1

Frequencies

GnomAD3 genomes AF: 0.000690 AC: 105 AN: 152158 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00137 AC: 343 AN: 251280 Hom.: 2 AF XY: 0.00122 AC XY: 166 AN XY: 135810

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00642

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.000924

Gnomad SAS exome AF: 0.00170

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000326

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000510 AC: 745 AN: 1461758 Hom.: 1 Cov.: 31 AF XY: 0.000528 AC XY: 384 AN XY: 727184

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.00648

Gnomad4 ASJ exome AF: 0.000650

Gnomad4 EAS exome AF: 0.00134

Gnomad4 SAS exome AF: 0.00198

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000161

Gnomad4 OTH exome AF: 0.000464

GnomAD4 genome AF: 0.000690 AC: 105 AN: 152276 Hom.: 2 Cov.: 32 AF XY: 0.000846 AC XY: 63 AN XY: 74454

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.00431

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000346 Hom.: 1

Bravo AF: 0.00104

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00116 AC: 141

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
Cadd	Pathogenic	29
Dann	Uncertain	0.98
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D
MetaRNN	Benign	0.0089	T;T;T;T;T;T
MetaSVM	Benign	-0.65	T
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.55	T;T;T;T;T;T
Sift4G	Benign	0.54	T;T;T;T;T;T
Polyphen		1.0	D;D;D;D;D;D
Vest4		0.31
MVP		0.67
MPC		0.67
ClinPred		0.10	T
GERP RS		4.0
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.10
gMVP		0.52

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

LitVar

Other links and lift over

dbSNP: rs74387785; hg19: chr4-89668798; COSMIC: COSV104386604; COSMIC: COSV104386604;