rs573248684

Variant names:

• chr19-19120843-A-C
• rs573248684
• NM_017814.3:c.1108T>G

Your query was ambiguous. Multiple possible variants found:

• chr19-19120843-A-C
• chr19-19120843-A-G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_017814.3(TMEM161A):​c.1108T>G​(p.Tyr370Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. Y370H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM161A NM_017814.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.34
• Publications: 1 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.979

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM161A	NM_017814.3	c.1108T>G	p.Tyr370Asp	missense_variant	Exon 11 of 12	ENST00000162044.14	NP_060284.1
TMEM161A	NM_001411131.1	c.1033T>G	p.Tyr345Asp	missense_variant	Exon 11 of 12		NP_001398060.1
TMEM161A	NM_001256766.3	c.799T>G	p.Tyr267Asp	missense_variant	Exon 9 of 10		NP_001243695.1
TMEM161A	XM_047439023.1	c.1057T>G	p.Tyr353Asp	missense_variant	Exon 11 of 12		XP_047294979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM161A	ENST00000162044.14	c.1108T>G	p.Tyr370Asp	missense_variant	Exon 11 of 12	1	NM_017814.3	ENSP00000162044.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.56	.;D;T
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Pathogenic	0.42	D
MetaRNN	Pathogenic	0.98	D;D;D
MetaSVM	Uncertain	-0.038	T
MutationAssessor	Uncertain	2.8	.;M;.
PhyloP100		6.3
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-8.3	D;D;.
REVEL	Pathogenic	0.74
Sift	Pathogenic	0.0	D;D;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.91
MutPred		0.90		.;Loss of MoRF binding (P = 0.0745);.;
MVP		0.51
MPC		1.2
ClinPred		1.0	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.93
gMVP		0.89
Mutation Taster		=23/77	disease causing

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: rs573248684; hg19: chr19-19231652;