rs781737745

Variant names:

• chr19-19121395-G-A
• rs781737745
• NM_017814.3:c.827C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-19121395-G-A
• chr19-19121395-G-T

Variant summary

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

The NM_017814.3(TMEM161A):​c.827C>T​(p.Ser276Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,702 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S276Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMEM161A NM_017814.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.01
• Publications: 0 publications found

Genes affected

TMEM161A (HGNC:26020): (transmembrane protein 161A) Involved in several processes, including cellular response to UV; regulation of response to DNA damage stimulus; and response to retinoic acid. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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
TMEM161A	NM_017814.3	c.827C>T	p.Ser276Phe	missense_variant	Exon 9 of 12	ENST00000162044.14	NP_060284.1
TMEM161A	NM_001411131.1	c.752C>T	p.Ser251Phe	missense_variant	Exon 9 of 12		NP_001398060.1
TMEM161A	NM_001256766.3	c.518C>T	p.Ser173Phe	missense_variant	Exon 7 of 10		NP_001243695.1
TMEM161A	XM_047439023.1	c.776C>T	p.Ser259Phe	missense_variant	Exon 9 of 12		XP_047294979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM161A	ENST00000162044.14	c.827C>T	p.Ser276Phe	missense_variant	Exon 9 of 12	1	NM_017814.3	ENSP00000162044.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460702 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726612

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39588

South Asian (SAS) AF: 0.00 AC: 0 AN: 86110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111536

Other (OTH) AF: 0.00 AC: 0 AN: 60344

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	.;T;T;T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.4	.;M;.;.
PhyloP100		7.0
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.5	D;N;.;.
REVEL	Benign	0.22
Sift	Benign	0.54	T;T;.;.
Sift4G	Uncertain	0.0080	D;D;D;.
Polyphen		0.97	.;D;.;.
Vest4		0.54
MutPred		0.75		.;Loss of catalytic residue at S276 (P = 0.0425);.;.;
MVP		0.34
MPC		0.89
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.19
gMVP		0.68
Mutation Taster		=57/43	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: rs781737745; hg19: chr19-19232204;