5-137943212-G-C

Variant names:

• chr5-137943212-G-C
• NM_001385994.1:c.2345C>G

Variant summary

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

The NM_001385994.1(FAM13B):​c.2345C>G​(p.Ser782Cys) 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: FAM13B NM_001385994.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.42
• Publications: 0 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.2345C>G	p.Ser782Cys	missense	Exon 21 of 24	NP_001372923.1	A0A8I5KSB9
	FAM13B	NM_001385921.1		c.2279C>G	p.Ser760Cys	missense	Exon 21 of 24	NP_001372850.1	A0A2X0SG06
	FAM13B	NM_016603.4		c.2279C>G	p.Ser760Cys	missense	Exon 20 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.2345C>G	p.Ser782Cys	missense	Exon 21 of 24	ENSP00000509788.1	A0A8I5KSB9
	FAM13B	ENST00000033079.7	TSL:1	c.2279C>G	p.Ser760Cys	missense	Exon 20 of 23	ENSP00000033079.3	Q9NYF5-1
	FAM13B	ENST00000420893.6	TSL:1	c.2195C>G	p.Ser732Cys	missense	Exon 19 of 22	ENSP00000388521.2	Q9NYF5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Uncertain	0.36
BayesDel_addAF	Benign	-0.0030	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		9.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.015	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.44		Loss of disorder (P = 0.0073)
MVP		0.32
MPC		0.54
ClinPred		0.97	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.43
Mutation Taster		=32/68	disease causing

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

hg19: chr5-137278901;