1-205084091-C-T

Variant names:

• chr1-205084091-C-T
• rs4951168
• NM_203376.2:c.230G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203376.2(TMEM81):​c.230G>A​(p.Arg77Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 1,613,970 control chromosomes in the GnomAD database, including 602,838 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.80 (49799 hom., cov: 31)
  • Exomes 𝑓: 0.87 (553039 hom.)
• Consequence: TMEM81 NM_203376.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254

Genes affected

TMEM81 (HGNC:32349): (transmembrane protein 81) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.531576E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM81	NM_203376.2	c.230G>A	p.Arg77Gln	missense_variant	Exon 1 of 1	ENST00000367167.4	NP_976310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM81	ENST00000367167.4	c.230G>A	p.Arg77Gln	missense_variant	Exon 1 of 1	6	NM_203376.2	ENSP00000356135.3

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121526 AN: 151978 Hom.: 49783 Cov.: 31

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.912

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.841

GnomAD3 exomes AF: 0.871 AC: 219028 AN: 251438 Hom.: 96282 AF XY: 0.874 AC XY: 118824 AN XY: 135896

Gnomad AFR exome AF: 0.592

Gnomad AMR exome AF: 0.924

Gnomad ASJ exome AF: 0.864

Gnomad EAS exome AF: 0.973

Gnomad SAS exome AF: 0.908

Gnomad FIN exome AF: 0.893

Gnomad NFE exome AF: 0.865

Gnomad OTH exome AF: 0.874

GnomAD4 exome AF: 0.868 AC: 1269115 AN: 1461874 Hom.: 553039 Cov.: 69 AF XY: 0.869 AC XY: 632194 AN XY: 727240

Gnomad4 AFR exome AF: 0.575

Gnomad4 AMR exome AF: 0.921

Gnomad4 ASJ exome AF: 0.857

Gnomad4 EAS exome AF: 0.967

Gnomad4 SAS exome AF: 0.903

Gnomad4 FIN exome AF: 0.891

Gnomad4 NFE exome AF: 0.868

Gnomad4 OTH exome AF: 0.861

GnomAD4 genome AF: 0.799 AC: 121581 AN: 152096 Hom.: 49799 Cov.: 31 AF XY: 0.803 AC XY: 59726 AN XY: 74348

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.863

Gnomad4 EAS AF: 0.970

Gnomad4 SAS AF: 0.912

Gnomad4 FIN AF: 0.889

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.843

Alfa AF: 0.853 Hom.: 122163

Bravo AF: 0.793

TwinsUK AF: 0.864 AC: 3204

ALSPAC AF: 0.874 AC: 3369

ESP6500AA AF: 0.603 AC: 2657

ESP6500EA AF: 0.863 AC: 7424

ExAC AF: 0.864 AC: 104938

Asia WGS AF: 0.928 AC: 3226 AN: 3478

EpiCase AF: 0.862

EpiControl AF: 0.861

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.75
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	6.5e-7	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.9	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.097
Sift	Benign	1.0	T
Sift4G	Benign	0.75	T
Polyphen		0.0	B
Vest4		0.029
MPC		0.078
ClinPred		0.0081	T
GERP RS		5.5
Varity_R		0.025
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4951168; hg19: chr1-205053219;