rs372278877

Variant names:

• chr7-73865191-G-A
• rs372278877
• NM_182504.4:c.271G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-73865191-G-A
• chr7-73865191-G-C

Variant summary

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

The NM_182504.4(TMEM270):​c.271G>A​(p.Val91Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. V91L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TMEM270 NM_182504.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• 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: 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=0.1833435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM270	NM_182504.4	c.271G>A	p.Val91Met	missense_variant	Exon 2 of 3	ENST00000320531.3	NP_872310.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM270	ENST00000320531.3	c.271G>A	p.Val91Met	missense_variant	Exon 2 of 3	1	NM_182504.4	ENSP00000316775.2
TMEM270	ENST00000426490.1	n.*211G>A		non_coding_transcript_exon_variant	Exon 3 of 4	5		ENSP00000403621.1
TMEM270	ENST00000426490.1	n.*211G>A		3_prime_UTR_variant	Exon 3 of 4	5		ENSP00000403621.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461478 Hom.: 0 Cov.: 67 AF XY: 0.00000413 AC XY: 3 AN XY: 727006

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53170

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

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111916

Other (OTH) AF: 0.00 AC: 0 AN: 60378

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	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0058	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.99	T
PhyloP100		1.1
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.080
Sift	Benign	0.10	T
Sift4G	Benign	0.18	T
Polyphen		0.93	P
Vest4		0.29
MutPred		0.28		Gain of MoRF binding (P = 0.0986);
MVP		0.048
MPC		0.11
ClinPred		0.54	D
GERP RS		0.58
Varity_R		0.050
gMVP		0.025
Mutation Taster		=99/1	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: rs372278877; hg19: chr7-73279521;