6-3849918-C-T

Variant names:

• chr6-3849918-C-T
• rs768869122
• NM_012135.3:c.107C>T

Variant summary

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

The NM_012135.3(FAM50B):​c.107C>T​(p.Ala36Val) variant causes a missense change. 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: 33)
• Consequence: FAM50B NM_012135.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.78

Genes affected

FAM50B (HGNC:18789): (family with sequence similarity 50 member B) This gene contains an intronless ORF that arose from ancestral retroposition. The encoded protein is related to a plant protein that plays a role in the circadian clock. This gene is adjacent to a differentially methylated region (DMR) and is imprinted and paternally expressed in many tissues. [provided by RefSeq, Nov 2015]

ENSG00000238158 (HGNC:):

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=0.18291381).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM50B	NM_012135.3	c.107C>T	p.Ala36Val	missense_variant	Exon 2 of 2	ENST00000648326.1	NP_036267.1
FAM50B	XM_017010729.2	c.107C>T	p.Ala36Val	missense_variant	Exon 2 of 2		XP_016866218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM50B	ENST00000648326.1	c.107C>T	p.Ala36Val	missense_variant	Exon 2 of 2		NM_012135.3	ENSP00000496837.1
FAM50B	ENST00000380274.2	c.107C>T	p.Ala36Val	missense_variant	Exon 1 of 1	6		ENSP00000369627.1
ENSG00000238158	ENST00000454396.2	n.80-5552C>T		intron_variant	Intron 1 of 1	5
ENSG00000233068	ENST00000648025.1	n.76+17907C>T		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.107C>T (p.A36V) alteration is located in exon 2 (coding exon 1) of the FAM50B gene. This alteration results from a C to T substitution at nucleotide position 107, causing the alanine (A) at amino acid position 36 to be replaced by a valine (V). 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	0.16
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T;T;T
Eigen	Benign	-0.058
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	.;.;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M;M
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.4	.;N;N
REVEL	Benign	0.070
Sift	Benign	0.079	.;T;T
Sift4G	Benign	0.25	.;T;T
Polyphen		0.017	B;B;B
Vest4		0.21, 0.25
MutPred		0.13		Gain of MoRF binding (P = 0.1164);Gain of MoRF binding (P = 0.1164);Gain of MoRF binding (P = 0.1164);
MVP		0.31
MPC		0.84
ClinPred		0.57	D
GERP RS		4.2
Varity_R		0.24
gMVP		0.88

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: rs768869122; hg19: chr6-3850152;