17-7355272-C-A

Variant names:

• chr17-7355272-C-A
• NM_001320436.2:c.68C>A

Variant summary

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

The NM_001320436.2(TMEM95):​c.68C>A​(p.Pro23Gln) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM95 NM_001320436.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.358

Genes affected

TMEM95 (HGNC:27898): (transmembrane protein 95) Predicted to be involved in fusion of sperm to egg plasma membrane involved in single fertilization. Predicted to be located in sperm plasma membrane. Predicted to be integral component of membrane. Predicted to be active in acrosomal membrane. [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=0.10098076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM95	NM_001320436.2	c.68C>A	p.Pro23Gln	missense_variant	Exon 1 of 7	ENST00000576060.6	NP_001307365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM95	ENST00000576060.6	c.68C>A	p.Pro23Gln	missense_variant	Exon 1 of 7	1	NM_001320436.2	ENSP00000460828.1
TMEM95	ENST00000389982.8	c.68C>A	p.Pro23Gln	missense_variant	Exon 1 of 7	1		ENSP00000374632.4
TMEM95	ENST00000330767.4	c.68C>A	p.Pro23Gln	missense_variant	Exon 1 of 7	1		ENSP00000331466.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 16, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.68C>A (p.P23Q) alteration is located in exon 1 (coding exon 1) of the TMEM95 gene. This alteration results from a C to A substitution at nucleotide position 68, causing the proline (P) at amino acid position 23 to be replaced by a glutamine (Q). 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	0.21
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	.;T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.61	T;T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-6.2	D;.;D
REVEL	Benign	0.057
Sift	Benign	0.081	T;.;T
Sift4G	Benign	0.12	T;T;T
Polyphen		0.30	B;B;B
Vest4		0.38
MutPred		0.40		Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);
MVP		0.061
MPC		0.20
ClinPred		0.37	T
GERP RS		2.9
Varity_R		0.035
gMVP		0.35

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: chr17-7258591;