5-137943204-T-G

Variant names:

• chr5-137943204-T-G
• rs1282985348
• NM_001385994.1:c.2353A>C

Variant summary

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

The NM_001385994.1(FAM13B):​c.2353A>C​(p.Thr785Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,158 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM13B NM_001385994.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.61

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=0.26141566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM13B	NM_001385994.1	c.2353A>C	p.Thr785Pro	missense_variant	Exon 21 of 24	ENST00000689681.1	NP_001372923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM13B	ENST00000689681.1	c.2353A>C	p.Thr785Pro	missense_variant	Exon 21 of 24		NM_001385994.1	ENSP00000509788.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461158 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726976

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000662 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2287A>C (p.T763P) alteration is located in exon 20 (coding exon 18) of the FAM13B gene. This alteration results from a A to C substitution at nucleotide position 2287, causing the threonine (T) at amino acid position 763 to be replaced by a proline (P). 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	0.14
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.4	N;N;N
REVEL	Benign	0.20
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.040	D;T;T
Polyphen		1.0	D;.;D
Vest4		0.23
MVP		0.11
MPC		0.31
ClinPred		0.78	D
GERP RS		5.9
Varity_R		0.45
gMVP		0.29

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: rs1282985348; hg19: chr5-137278893;