NM_001320436.2:c.365A>T

Variant names:

• chr17-7356232-A-T
• NM_001320436.2:c.365A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001320436.2(TMEM95):​c.365A>T​(p.Lys122Met) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TMEM95 NM_001320436.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.432
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.097010046).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320436.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM95	NM_001320436.2	MANE Select	c.365A>T	p.Lys122Met	missense	Exon 5 of 7	NP_001307365.1	Q3KNT9-1
	TMEM95	NM_001320435.2		c.365A>T	p.Lys122Met	missense	Exon 5 of 7	NP_001307364.1	Q3KNT9-3
	TMEM95	NM_198154.3		c.389A>T	p.Lys130Met	missense	Exon 5 of 7	NP_937797.1	Q3KNT9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM95	ENST00000576060.6	TSL:1 MANE Select	c.365A>T	p.Lys122Met	missense	Exon 5 of 7	ENSP00000460828.1	Q3KNT9-1
	TMEM95	ENST00000389982.8	TSL:1	c.365A>T	p.Lys122Met	missense	Exon 5 of 7	ENSP00000374632.4	Q3KNT9-3
	TMEM95	ENST00000330767.4	TSL:1	c.389A>T	p.Lys130Met	missense	Exon 5 of 7	ENSP00000331466.4	Q3KNT9-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.3
DANN	Benign	0.76
DEOGEN2	Benign	0.19	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.43
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.070
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.014	D
Polyphen		0.79	P
Vest4		0.36
MutPred		0.27		Loss of methylation at K122 (P = 0.003)
MVP		0.072
MPC		0.040
ClinPred		0.46	T
GERP RS		-6.6
Varity_R		0.091
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr17-7259551;