chr19-19120117-G-T

Variant names:

• chr19-19120117-G-T
• rs769214375
• NM_017814.3:c.1253C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017814.3(TMEM161A):​c.1253C>A​(p.Ala418Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A418V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TMEM161A NM_017814.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.079827696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM161A	NM_017814.3	c.1253C>A	p.Ala418Asp	missense_variant	Exon 12 of 12	ENST00000162044.14	NP_060284.1
TMEM161A	NM_001411131.1	c.1178C>A	p.Ala393Asp	missense_variant	Exon 12 of 12		NP_001398060.1
TMEM161A	NM_001256766.3	c.944C>A	p.Ala315Asp	missense_variant	Exon 10 of 10		NP_001243695.1
TMEM161A	XM_047439023.1	c.1202C>A	p.Ala401Asp	missense_variant	Exon 12 of 12		XP_047294979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM161A	ENST00000162044.14	c.1253C>A	p.Ala418Asp	missense_variant	Exon 12 of 12	1	NM_017814.3	ENSP00000162044.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000576 AC: 1 AN: 173748 AF XY: 0.0000107

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000746

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416876 Hom.: 0 Cov.: 37 AF XY: 0.00000143 AC XY: 1 AN XY: 700444

African (AFR) AF: 0.00 AC: 0 AN: 32668

American (AMR) AF: 0.00 AC: 0 AN: 37298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25264

East Asian (EAS) AF: 0.0000266 AC: 1 AN: 37618

South Asian (SAS) AF: 0.00 AC: 0 AN: 80682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49884

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5450

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1089290

Other (OTH) AF: 0.00 AC: 0 AN: 58722

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	1.9
DANN	Benign	0.46
DEOGEN2	Benign	0.016	.;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.41	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.080	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	.;L;.
PhyloP100		0.48
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.99	N;N;.
REVEL	Benign	0.039
Sift	Benign	0.63	T;T;.
Sift4G	Benign	0.61	T;T;T
Polyphen		0.16	.;B;.
Vest4		0.076
MutPred		0.37		.;Loss of stability (P = 0.0521);.;
MVP		0.12
MPC		0.40
ClinPred		0.064	T
GERP RS		-6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.085
gMVP		0.41
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs769214375; hg19: chr19-19230926;