NM_001385994.1:c.1845C>G

Variant names:

• chr5-137953339-G-C
• NM_001385994.1:c.1845C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001385994.1(FAM13B):​c.1845C>G​(p.Ser615Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 0.719

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22218531).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM13B	NM_001385994.1	c.1845C>G	p.Ser615Arg	missense_variant	Exon 16 of 24	ENST00000689681.1	NP_001372923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM13B	ENST00000689681.1	c.1845C>G	p.Ser615Arg	missense_variant	Exon 16 of 24		NM_001385994.1	ENSP00000509788.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1779C>G (p.S593R) alteration is located in exon 15 (coding exon 13) of the FAM13B gene. This alteration results from a C to G substitution at nucleotide position 1779, causing the serine (S) at amino acid position 593 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.097	T;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.098
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Uncertain	0.54	D
MutationAssessor	Benign	1.1	L;.;L
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Uncertain	0.34
Sift	Uncertain	0.011	D;D;D
Sift4G	Benign	0.22	T;T;T
Polyphen		0.21	B;.;B
Vest4		0.40
MutPred		0.24		Loss of phosphorylation at S593 (P = 0.014);.;Loss of phosphorylation at S593 (P = 0.014);
MVP		0.32
MPC		0.16
ClinPred		0.61	D
GERP RS		3.3
Varity_R		0.077
gMVP		0.049

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-137289028;