5-88251742-T-C

Variant names:

• chr5-88251742-T-C
• rs390856
• NM_153354.5:c.4-10826A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153354.5(TMEM161B):​c.4-10826A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,100 control chromosomes in the GnomAD database, including 47,235 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (47235 hom., cov: 32)
• Consequence: TMEM161B NM_153354.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818
• Publications: 7 publications found

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]

TMEM161B Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153354.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM161B	NM_153354.5	MANE Select	c.4-10826A>G		intron	N/A	NP_699185.1
	TMEM161B	NM_001349407.2		c.4-10826A>G		intron	N/A	NP_001336336.1
	TMEM161B	NM_001289007.2		c.4-10826A>G		intron	N/A	NP_001275936.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM161B	ENST00000296595.11	TSL:1 MANE Select	c.4-10826A>G		intron	N/A	ENSP00000296595.6
	TMEM161B	ENST00000510089.5	TSL:1	n.-275+16979A>G		intron	N/A	ENSP00000423380.1
	TMEM161B	ENST00000511087.5	TSL:1	n.4-10826A>G		intron	N/A	ENSP00000421805.1

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119596 AN: 151982 Hom.: 47198 Cov.: 32

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.802

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.787 AC: 119691 AN: 152100 Hom.: 47235 Cov.: 32 AF XY: 0.790 AC XY: 58753 AN XY: 74336

African (AFR) AF: 0.820 AC: 34028 AN: 41498

American (AMR) AF: 0.846 AC: 12915 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2664 AN: 3472

East Asian (EAS) AF: 0.806 AC: 4164 AN: 5166

South Asian (SAS) AF: 0.859 AC: 4145 AN: 4828

European-Finnish (FIN) AF: 0.741 AC: 7824 AN: 10562

Middle Eastern (MID) AF: 0.788 AC: 230 AN: 292

European-Non Finnish (NFE) AF: 0.755 AC: 51333 AN: 67992

Other (OTH) AF: 0.802 AC: 1695 AN: 2114

Alfa AF: 0.770 Hom.: 5432

Bravo AF: 0.795

Asia WGS AF: 0.851 AC: 2961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.34
DANN	Benign	0.34
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

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: rs390856; hg19: chr5-87547559;