chr7-73865290-G-T

Variant names:

• chr7-73865290-G-T
• rs557233860
• NM_182504.4:c.370G>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.370G>T​(p.Val124Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,050 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V124M) 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: -0.374
• 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=0.04828435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM270	NM_182504.4	c.370G>T	p.Val124Leu	missense_variant	Exon 2 of 3	ENST00000320531.3	NP_872310.2
TMEM270	XM_011515785.3	c.79G>T	p.Val27Leu	missense_variant	Exon 2 of 3		XP_011514087.1
TMEM270	XM_017011741.2	c.79G>T	p.Val27Leu	missense_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.370G>T	p.Val124Leu	missense_variant	Exon 2 of 3	1	NM_182504.4	ENSP00000316775.2
TMEM270	ENST00000426490.1	n.*310G>T		non_coding_transcript_exon_variant	Exon 3 of 4	5		ENSP00000403621.1
TMEM270	ENST00000426490.1	n.*310G>T		3_prime_UTR_variant	Exon 3 of 4	5		ENSP00000403621.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461050 Hom.: 0 Cov.: 68 AF XY: 0.00000138 AC XY: 1 AN XY: 726856

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52600

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.6
DANN	Benign	0.57
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0083	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.37
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.0060
Sift	Benign	0.23	T
Sift4G	Benign	0.34	T
Polyphen		0.0020	B
Vest4		0.062
MutPred		0.29		Loss of catalytic residue at V124 (P = 0.0762);
MVP		0.014
MPC		0.016
ClinPred		0.10	T
GERP RS		-0.22
Varity_R		0.088
gMVP		0.053
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs557233860; hg19: chr7-73279620;