NM_001320436.2:c.88C>G

Variant names:

• chr17-7355292-C-G
• rs575727765
• NM_001320436.2:c.88C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001320436.2(TMEM95):​c.88C>G​(p.Arg30Gly) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R30C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM95 NM_001320436.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.53
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.749

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.88C>G	p.Arg30Gly	missense	Exon 1 of 7	NP_001307365.1	Q3KNT9-1
	TMEM95	NM_001320435.2		c.88C>G	p.Arg30Gly	missense	Exon 1 of 7	NP_001307364.1	Q3KNT9-3
	TMEM95	NM_198154.3		c.88C>G	p.Arg30Gly	missense	Exon 1 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.88C>G	p.Arg30Gly	missense	Exon 1 of 7	ENSP00000460828.1	Q3KNT9-1
	TMEM95	ENST00000389982.8	TSL:1	c.88C>G	p.Arg30Gly	missense	Exon 1 of 7	ENSP00000374632.4	Q3KNT9-3
	TMEM95	ENST00000330767.4	TSL:1	c.88C>G	p.Arg30Gly	missense	Exon 1 of 7	ENSP00000331466.4	Q3KNT9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0052	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.5
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.38		Loss of methylation at R30 (P = 0.0231)
MVP		0.24
MPC		0.095
ClinPred		0.99	D
GERP RS		5.3
PromoterAI		0.067	Neutral
Varity_R		0.31
gMVP		0.64

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

Other links and lift over

dbSNP: rs575727765; hg19: chr17-7258611;