1-54991894-G-T

Variant names:

• chr1-54991894-G-T
• rs201375691
• NM_182532.3:c.424G>T

Variant summary

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

The NM_182532.3(TMEM61):​c.424G>T​(p.Glu142*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,170 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (1 hom., cov: 33)
• Consequence: TMEM61 NM_182532.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23
• Publications: 2 publications found

Genes affected

TMEM61 (HGNC:27296): (transmembrane protein 61) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

DHCR24-DT (HGNC:53969): (DHCR24 divergent transcript)

ENSG00000233271 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM61	NM_182532.3	c.424G>T	p.Glu142*	stop_gained	Exon 3 of 3	ENST00000371268.4	NP_872338.1
TMEM61	XM_011540911.3	c.424G>T	p.Glu142*	stop_gained	Exon 4 of 4		XP_011539213.1
TMEM61	XM_005270586.5	c.409G>T	p.Glu137*	stop_gained	Exon 3 of 3		XP_005270643.1
TMEM61	XM_011540912.3	c.409G>T	p.Glu137*	stop_gained	Exon 3 of 3		XP_011539214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM61	ENST00000371268.4	c.424G>T	p.Glu142*	stop_gained	Exon 3 of 3	1	NM_182532.3	ENSP00000360315.3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152170 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152170 Hom.: 1 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74336

African (AFR) AF: 0.0000483 AC: 2 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	35
DANN	Uncertain	0.98
Eigen	Uncertain	0.40
Eigen_PC	Benign	0.049
FATHMM_MKL	Benign	0.19	N
PhyloP100		2.2
Vest4		0.051
GERP RS		3.6
Mutation Taster		=101/99	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: rs201375691; hg19: chr1-55457567; COSMIC: COSV64873897;