1-46533014-G-A

Variant names:

• chr1-46533014-G-A
• rs546020419
• NM_001396071.1:c.514C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001396071.1(TMEM275):​c.514C>T​(p.Arg172Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 396,418 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (13 hom.)
• Consequence: TMEM275 NM_001396071.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.24

Genes affected

TMEM275 (HGNC:53938): (transmembrane protein 275) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0103928745).
• BP6: Variant 1-46533014-G-A is Benign according to our data. Variant chr1-46533014-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638800.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM275	NM_001396071.1	c.514C>T	p.Arg172Trp	missense_variant	Exon 4 of 4	ENST00000697682.1	NP_001383000.1
TMEM275	NM_001357063.3	c.514C>T	p.Arg172Trp	missense_variant	Exon 3 of 3		NP_001343992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM275	ENST00000697682.1	c.514C>T	p.Arg172Trp	missense_variant	Exon 4 of 4		NM_001396071.1	ENSP00000513394.1
TMEM275	ENST00000634804.2	c.514C>T	p.Arg172Trp	missense_variant	Exon 2 of 2	6		ENSP00000489149.1

Frequencies

GnomAD3 genomes AF: 0.00391 AC: 594 AN: 152016 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00870

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00571

Gnomad OTH AF: 0.00431

GnomAD4 exome AF: 0.00563 AC: 1376 AN: 244290 Hom.: 13 Cov.: 0 AF XY: 0.00558 AC XY: 692 AN XY: 123936

Gnomad4 AFR exome AF: 0.000425

Gnomad4 AMR exome AF: 0.00136

Gnomad4 ASJ exome AF: 0.00692

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000332

Gnomad4 FIN exome AF: 0.0158

Gnomad4 NFE exome AF: 0.00564

Gnomad4 OTH exome AF: 0.00537

GnomAD4 genome AF: 0.00390 AC: 594 AN: 152128 Hom.: 3 Cov.: 32 AF XY: 0.00387 AC XY: 288 AN XY: 74364

Gnomad4 AFR AF: 0.000866

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00870

Gnomad4 NFE AF: 0.00571

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00680 Hom.: 1

Bravo AF: 0.00297

Asia WGS AF: 0.00116 AC: 4 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TMEM275: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Benign	0.93
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.010	T
Sift4G	Uncertain	0.0070	D
Vest4		0.27
GERP RS		1.8
gMVP		0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs546020419; hg19: chr1-46998686;