5-88206464-G-A

Variant names:

• chr5-88206464-G-A
• rs1369444900
• NM_153354.5:c.634C>T

Variant summary

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

The NM_153354.5(TMEM161B):​c.634C>T​(p.Leu212Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000485 in 1,442,736 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: TMEM161B NM_153354.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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>T	p.Leu212Phe	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>T	p.Leu212Phe	missense_variant	Exon 7 of 12	1	NM_153354.5	ENSP00000296595.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000485 AC: 7 AN: 1442736 Hom.: 0 Cov.: 30 AF XY: 0.00000279 AC XY: 2 AN XY: 717156

Gnomad4 AFR exome AF: 0.0000305

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000363

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 01, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.634C>T (p.L212F) alteration is located in exon 7 (coding exon 7) of the TMEM161B gene. This alteration results from a C to T substitution at nucleotide position 634, causing the leucine (L) at amino acid position 212 to be replaced by a phenylalanine (F). 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	0.23
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	.;T;.;.;T;T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D
M_CAP	Benign	0.0059	T
MetaRNN	Uncertain	0.47	T;T;T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.7	.;L;.;.;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.4	D;D;D;D;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.011	D;D;D;D;D;D
Sift4G	Uncertain	0.026	D;D;D;D;D;T
Polyphen		0.0060	.;B;.;B;.;.
Vest4		0.51
MutPred		0.80		Gain of methylation at K214 (P = 0.1047);Gain of methylation at K214 (P = 0.1047);.;.;.;.;
MVP		0.12
MPC		0.24
ClinPred		0.53	D
GERP RS		5.5
Varity_R		0.43
gMVP		0.66

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

LitVar

Other links and lift over

dbSNP: rs1369444900; hg19: chr5-87502281;