rs772160288

Variant names:

• chr5-137949140-G-A
• rs772160288
• NM_001385994.1:c.1975C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-137949140-G-A
• chr5-137949140-G-T

Variant summary

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

The NM_001385994.1(FAM13B):​c.1975C>T​(p.Arg659Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R659S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: FAM13B NM_001385994.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60
• Publications: 3 publications found

Genes affected

FAM13B (HGNC:1335): (family with sequence similarity 13 member B) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385994.1. 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
	FAM13B	NM_001385994.1	MANE Select	c.1975C>T	p.Arg659Cys	missense	Exon 18 of 24	NP_001372923.1	A0A8I5KSB9
	FAM13B	NM_001385921.1		c.1909C>T	p.Arg637Cys	missense	Exon 18 of 24	NP_001372850.1	A0A2X0SG06
	FAM13B	NM_016603.4		c.1909C>T	p.Arg637Cys	missense	Exon 17 of 23	NP_057687.2	A0A2X0SG06

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM13B	ENST00000689681.1	MANE Select	c.1975C>T	p.Arg659Cys	missense	Exon 18 of 24	ENSP00000509788.1	A0A8I5KSB9
	FAM13B	ENST00000033079.7	TSL:1	c.1909C>T	p.Arg637Cys	missense	Exon 17 of 23	ENSP00000033079.3	Q9NYF5-1
	FAM13B	ENST00000420893.6	TSL:1	c.1909C>T	p.Arg637Cys	missense	Exon 17 of 22	ENSP00000388521.2	Q9NYF5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 250804 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1461818 Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.000134 AC: 6 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

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

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000824 AC: 1

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	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		9.6
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.17		Loss of phosphorylation at S640 (P = 0.0703)
MVP		0.36
MPC		0.63
ClinPred		0.93	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.25
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs772160288; hg19: chr5-137284829; COSMIC: COSV50373117; COSMIC: COSV50373117;