chr19-19121038-A-T

Variant names:

• chr19-19121038-A-T
• rs1663293396
• NM_017814.3:c.1043T>A

Variant summary

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

The NM_017814.3(TMEM161A):​c.1043T>A​(p.Leu348Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM161A NM_017814.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.47
• 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.1043T>A	p.Leu348Gln	missense_variant	Exon 10 of 12	ENST00000162044.14	NP_060284.1
TMEM161A	NM_001411131.1	c.968T>A	p.Leu323Gln	missense_variant	Exon 10 of 12		NP_001398060.1
TMEM161A	NM_001256766.3	c.734T>A	p.Leu245Gln	missense_variant	Exon 8 of 10		NP_001243695.1
TMEM161A	XM_047439023.1	c.992T>A	p.Leu331Gln	missense_variant	Exon 10 of 12		XP_047294979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM161A	ENST00000162044.14	c.1043T>A	p.Leu348Gln	missense_variant	Exon 10 of 12	1	NM_017814.3	ENSP00000162044.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1043T>A (p.L348Q) alteration is located in exon 10 (coding exon 10) of the TMEM161A gene. This alteration results from a T to A substitution at nucleotide position 1043, causing the leucine (L) at amino acid position 348 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	.;T;T;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D;D;T
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.73	D;D;D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.2	.;L;.;.
PhyloP100		8.5
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.1	N;N;.;.
REVEL	Benign	0.28
Sift	Benign	0.52	T;T;.;.
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		0.98	.;D;.;.
Vest4		0.61
MutPred		0.74		.;Gain of disorder (P = 0.0093);.;.;
MVP		0.36
MPC		0.88
ClinPred		0.92	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.62
Mutation Taster		=28/72	disease causing

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

Other links and lift over

dbSNP: rs1663293396; hg19: chr19-19231847;