chr15-68290889-A-C

Position:

• chr15-68290889-A-C

Variant summary

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

The NM_015322.5(FEM1B):​c.1531A>C​(p.Asn511His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.25

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEM1B	NM_015322.5	c.1531A>C	p.Asn511His	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.1531A>C	p.Asn511His	missense_variant	2/2	1	NM_015322.5	ENSP00000307298	P1
FEM1B	ENST00000566008.1	c.457A>C	p.Asn153His	missense_variant	2/2	2		ENSP00000456968

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

May 29, 2024

The c.1531A>C (p.N511H) alteration is located in exon 2 (coding exon 2) of the FEM1B gene. This alteration results from a A to C substitution at nucleotide position 1531, causing the asparagine (N) at amino acid position 511 to be replaced by a histidine (H). 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	0.26
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	0.73	D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.31
Sift	Benign	0.12	T
Sift4G	Benign	0.17	T
Polyphen		0.83	P
Vest4		0.53
MutPred		0.64		Gain of catalytic residue at L513 (P = 0.0618);
MVP		0.49
MPC		1.9
ClinPred		0.77	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.21
gMVP		0.75

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: chr15-68583227;