15-68289870-G-C

Position:

• chr15-68289870-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015322.5(FEM1B):​c.512G>C​(p.Arg171Thr) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FEM1B NM_015322.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.83

Genes affected

FEM1B (HGNC:3649): (fem-1 homolog B) This gene encodes an ankyrin repeat protein that belongs to the death receptor-associated family of proteins and plays a role in mediating apoptosis. The encoded protein is also thought to function in the replication stress-induced checkpoint signaling pathway via interaction with checkpoint kinase 1. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32376796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEM1B	NM_015322.5	c.512G>C	p.Arg171Thr	missense_variant	2/2	ENST00000306917.5	NP_056137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FEM1B	ENST00000306917.5	c.512G>C	p.Arg171Thr	missense_variant	2/2	1	NM_015322.5	ENSP00000307298	P1
FEM1B	ENST00000566739.1	c.38G>C	p.Arg13Thr	missense_variant	2/2	4		ENSP00000457342
FEM1B	ENST00000570067.1			downstream_gene_variant		4		ENSP00000457002

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2022

The c.512G>C (p.R171T) alteration is located in exon 2 (coding exon 2) of the FEM1B gene. This alteration results from a G to C substitution at nucleotide position 512, causing the arginine (R) at amino acid position 171 to be replaced by a threonine (T). 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	0.11
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Benign	0.89
DEOGEN2	Benign	0.18	T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.0043
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.31
Sift	Benign	0.27	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.0020	B;.
Vest4		0.59
MutPred		0.63		Gain of glycosylation at R171 (P = 0.1618);.;
MVP		0.89
MPC		1.5
ClinPred		0.18	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.24
gMVP		0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-68582208;