5-88206464-G-T

Variant names:

• chr5-88206464-G-T
• NM_153354.5:c.634C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153354.5(TMEM161B):​c.634C>A​(p.Leu212Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,442,740 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. L212F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TMEM161B NM_153354.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.31

Genes affected

TMEM161B (HGNC:28483): (transmembrane protein 161B) Predicted to enable nucleic acid binding activity. Predicted to be involved in DNA integration. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
TMEM161B	NM_153354.5	c.634C>A	p.Leu212Ile	missense_variant	Exon 7 of 12	ENST00000296595.11	NP_699185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM161B	ENST00000296595.11	c.634C>A	p.Leu212Ile	missense_variant	Exon 7 of 12	1	NM_153354.5	ENSP00000296595.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442740 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 717158

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.060	.;T;.;.;T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;D
M_CAP	Benign	0.0075	T
MetaRNN	Uncertain	0.46	T;T;T;T;T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.6	.;M;.;.;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.7	N;N;N;N;N;N
REVEL	Uncertain	0.42
Sift	Uncertain	0.0070	D;D;D;D;D;D
Sift4G	Uncertain	0.015	D;D;D;D;D;D
Polyphen		0.47	.;P;.;P;.;.
Vest4		0.60
MutPred		0.74		Gain of catalytic residue at L212 (P = 0.026);Gain of catalytic residue at L212 (P = 0.026);.;.;.;.;
MVP		0.16
MPC		0.49
ClinPred		0.94	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.39

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-87502281;