7-73865182-G-T

Variant names:

• chr7-73865182-G-T
• rs782084386
• NM_182504.4:c.262G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182504.4(TMEM270):​c.262G>T​(p.Val88Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. V88I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMEM270 NM_182504.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 0 publications found

Genes affected

TMEM270 (HGNC:23018): (transmembrane protein 270) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0445984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM270	NM_182504.4	c.262G>T	p.Val88Leu	missense_variant	Exon 2 of 3	ENST00000320531.3	NP_872310.2
TMEM270	XM_011515785.3	c.-30G>T		5_prime_UTR_variant	Exon 2 of 3		XP_011514087.1
TMEM270	XM_017011741.2	c.-30G>T		5_prime_UTR_variant	Exon 2 of 3		XP_016867230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM270	ENST00000320531.3	c.262G>T	p.Val88Leu	missense_variant	Exon 2 of 3	1	NM_182504.4	ENSP00000316775.2
TMEM270	ENST00000426490.1	n.*202G>T		non_coding_transcript_exon_variant	Exon 3 of 4	5		ENSP00000403621.1
TMEM270	ENST00000426490.1	n.*202G>T		3_prime_UTR_variant	Exon 3 of 4	5		ENSP00000403621.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460856 Hom.: 0 Cov.: 67 AF XY: 0.00 AC XY: 0 AN XY: 726668

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111408

Other (OTH) AF: 0.00 AC: 0 AN: 60340

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.046
DANN	Benign	0.72
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.1
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.018
Sift	Benign	0.73	T
Sift4G	Benign	0.53	T
Polyphen		0.32	B
Vest4		0.048
MutPred		0.31		Loss of catalytic residue at V88 (P = 0.0864);
MVP		0.030
MPC		0.017
ClinPred		0.097	T
GERP RS		-1.9
Varity_R		0.050
gMVP		0.050
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs782084386; hg19: chr7-73279512;