5-88225798-G-T

Variant names:

• chr5-88225798-G-T
• NM_153354.5:c.260C>A

Variant summary

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

The NM_153354.5(TMEM161B):​c.260C>A​(p.Thr87Lys) 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM161B NM_153354.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.43

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.260C>A	p.Thr87Lys	missense_variant	Exon 4 of 12	ENST00000296595.11	NP_699185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM161B	ENST00000296595.11	c.260C>A	p.Thr87Lys	missense_variant	Exon 4 of 12	1	NM_153354.5	ENSP00000296595.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1458112 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 725476

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.260C>A (p.T87K) alteration is located in exon 4 (coding exon 4) of the TMEM161B gene. This alteration results from a C to A substitution at nucleotide position 260, causing the threonine (T) at amino acid position 87 to be replaced by a lysine (K). 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	0.19
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.099	.;T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.9	.;L;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Uncertain	0.39
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.99	.;D;.
Vest4		0.69
MutPred		0.59		Gain of solvent accessibility (P = 0.0156);Gain of solvent accessibility (P = 0.0156);.;
MVP		0.099
MPC		0.81
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.59
gMVP		0.72

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: chr5-87521615;