dbSNP rs763869369: FAM13B:p.Ile642Met (chr5-137952632-A-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001385994.1(FAM13B):c.1926T>G(p.Ile642Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000277 in 1,588,776 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

FAM13B
NM_001385994.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.148

Variant links:

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]

FAM13B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM13B	NM_001385994.1 link	c.1926T>G	p.Ile642Met	missense_variant	Exon 17 of 24	ENST00000689681.1	NP_001372923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAM13B	ENST00000689681.1 link	c.1926T>G	p.Ile642Met	missense_variant	Exon 17 of 24		NM_001385994.1	ENSP00000509788.1	A0A8I5KSB9
FAM13B	ENST00000033079.7 link	c.1860T>G	p.Ile620Met	missense_variant	Exon 16 of 23	1		ENSP00000033079.3	Q9NYF5-1
FAM13B	ENST00000420893.6 link	c.1860T>G	p.Ile620Met	missense_variant	Exon 16 of 22	1		ENSP00000388521.2	Q9NYF5-2
FAM13B	ENST00000425075.6 link	c.1572T>G	p.Ile524Met	missense_variant	Exon 16 of 22	1		ENSP00000394669.2	Q9NYF5-3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000330

AC:

AN:

242292

Hom.:

AF XY:

0.0000305

AC XY:

AN XY:

131104

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000626

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000538

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000278

AC:

AN:

1436544

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

714224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000937

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000255

Gnomad4 OTH exome

AF:

0.000135

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1860T>G (p.I620M) alteration is located in exon 16 (coding exon 14) of the FAM13B gene. This alteration results from a T to G substitution at nucleotide position 1860, causing the isoleucine (I) at amino acid position 620 to be replaced by a methionine (M). 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

Benign

0.12

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

T;.;.

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.45

T;T;T

MetaSVM

Uncertain

0.54

MutationAssessor

Uncertain

2.0

M;.;M

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.1

N;N;N

REVEL

Uncertain

0.42

Sift

Uncertain

0.0050

D;D;D

Sift4G

Benign

0.12

T;D;T

Polyphen

1.0

D;.;D

Vest4

0.61

MutPred

0.27

Gain of disorder (P = 0.0819);.;Gain of disorder (P = 0.0819);

MVP

0.68

MPC

0.22

ClinPred

0.36

GERP RS

0.61

Varity_R

0.25

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over