7-73865075-A-G

Variant names:

• chr7-73865075-A-G
• rs145787430
• NM_182504.4:c.155A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_182504.4(TMEM270):​c.155A>G​(p.Gln52Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,544,580 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (15 hom.)
• Consequence: TMEM270 NM_182504.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.272
• Publications: 5 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008065939).
• BP6: Variant 7-73865075-A-G is Benign according to our data. Variant chr7-73865075-A-G is described in ClinVar as [Benign]. Clinvar id is 3388115.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM270	NM_182504.4	c.155A>G	p.Gln52Arg	missense_variant	Exon 2 of 3	ENST00000320531.3	NP_872310.2
TMEM270	XM_011515785.3	c.-137A>G		5_prime_UTR_variant	Exon 2 of 3		XP_011514087.1
TMEM270	XM_017011741.2	c.-137A>G		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.155A>G	p.Gln52Arg	missense_variant	Exon 2 of 3	1	NM_182504.4	ENSP00000316775.2
TMEM270	ENST00000426490.1	n.*95A>G		non_coding_transcript_exon_variant	Exon 3 of 4	5		ENSP00000403621.1
TMEM270	ENST00000426490.1	n.*95A>G		3_prime_UTR_variant	Exon 3 of 4	5		ENSP00000403621.1

Frequencies

GnomAD3 genomes AF: 0.00210 AC: 319 AN: 151636 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00920

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00199

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000575

Gnomad OTH AF: 0.00433

GnomAD2 exomes AF: 0.00282 AC: 562 AN: 198976 AF XY: 0.00269

Gnomad AFR exome AF: 0.0000674

Gnomad AMR exome AF: 0.00979

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00736

Gnomad FIN exome AF: 0.00163

Gnomad NFE exome AF: 0.00106

Gnomad OTH exome AF: 0.00352

GnomAD4 exome AF: 0.00123 AC: 1719 AN: 1392824 Hom.: 15 Cov.: 34 AF XY: 0.00127 AC XY: 873 AN XY: 685594

African (AFR) AF: 0.000161 AC: 5 AN: 31150

American (AMR) AF: 0.0119 AC: 405 AN: 34002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21604

East Asian (EAS) AF: 0.0102 AC: 398 AN: 38976

South Asian (SAS) AF: 0.00225 AC: 169 AN: 75168

European-Finnish (FIN) AF: 0.00218 AC: 111 AN: 51020

Middle Eastern (MID) AF: 0.000551 AC: 3 AN: 5448

European-Non Finnish (NFE) AF: 0.000491 AC: 529 AN: 1078190

Other (OTH) AF: 0.00173 AC: 99 AN: 57266

GnomAD4 genome AF: 0.00210 AC: 319 AN: 151756 Hom.: 5 Cov.: 33 AF XY: 0.00257 AC XY: 191 AN XY: 74182

African (AFR) AF: 0.000266 AC: 11 AN: 41412

American (AMR) AF: 0.0122 AC: 186 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00922 AC: 47 AN: 5100

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4788

European-Finnish (FIN) AF: 0.00199 AC: 21 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000575 AC: 39 AN: 67838

Other (OTH) AF: 0.00429 AC: 9 AN: 2100

Alfa AF: 0.00127 Hom.: 2

Bravo AF: 0.00245

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000610 AC: 5

ExAC AF: 0.00250 AC: 301

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TMEM270: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0081	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.27
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.039
Sift	Benign	0.092	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.87	P
Vest4		0.23
MVP		0.092
MPC		0.058
ClinPred		0.053	T
GERP RS		2.0
Varity_R		0.27
gMVP		0.23
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs145787430; hg19: chr7-73279405;