rs575727765

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-7355292-C-T
• chr17-7355292-C-G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001320436.2(TMEM95):​c.88C>T​(p.Arg30Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,614,070 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: TMEM95 NM_001320436.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.36769468).

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>T	p.Arg30Cys	missense	Exon 1 of 7	NP_001307365.1	Q3KNT9-1
	TMEM95	NM_001320435.2		c.88C>T	p.Arg30Cys	missense	Exon 1 of 7	NP_001307364.1	Q3KNT9-3
	TMEM95	NM_198154.3		c.88C>T	p.Arg30Cys	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>T	p.Arg30Cys	missense	Exon 1 of 7	ENSP00000460828.1	Q3KNT9-1
	TMEM95	ENST00000389982.8	TSL:1	c.88C>T	p.Arg30Cys	missense	Exon 1 of 7	ENSP00000374632.4	Q3KNT9-3
	TMEM95	ENST00000330767.4	TSL:1	c.88C>T	p.Arg30Cys	missense	Exon 1 of 7	ENSP00000331466.4	Q3KNT9-2

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152232 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000104 AC: 26 AN: 250618 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000619

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000135 AC: 197 AN: 1461720 Hom.: 1 Cov.: 33 AF XY: 0.000164 AC XY: 119 AN XY: 727162

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000754 AC: 65 AN: 86256

European-Finnish (FIN) AF: 0.0000937 AC: 5 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000110 AC: 122 AN: 1111940

Other (OTH) AF: 0.0000331 AC: 2 AN: 60380

GnomAD4 genome AF: 0.0000853 AC: 13 AN: 152350 Hom.: 0 Cov.: 32 AF XY: 0.0000805 AC XY: 6 AN XY: 74498

African (AFR) AF: 0.0000962 AC: 4 AN: 41580

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000138 Hom.: 0

Bravo AF: 0.0000831

ExAC AF: 0.0000988 AC: 12

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	Pathogenic	0.72
BayesDel_addAF	Benign	0.0034	T
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.5
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-7.7	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.68
MVP		0.22
MPC		0.21
ClinPred		0.69	D
GERP RS		5.3
PromoterAI		0.0024	Neutral
Varity_R		0.14
gMVP		0.57
Mutation Taster		=79/21	polymorphism

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;