chr5-88234436-A-C

Variant names:

• chr5-88234436-A-C
• rs247916
• NM_153354.5:c.108-5908T>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.108-5908T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,090 control chromosomes in the GnomAD database, including 7,326 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 0.28 (7326 hom., cov: 32)
• Consequence: TMEM161B NM_153354.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• 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 (AFR) allele frequency at 95% confidence interval = 0.46 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM161B	NM_153354.5	MANE Select	c.108-5908T>G		intron	N/A	NP_699185.1
	TMEM161B	NM_001349407.2		c.108-5908T>G		intron	N/A	NP_001336336.1
	TMEM161B	NM_001289007.2		c.108-5908T>G		intron	N/A	NP_001275936.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM161B	ENST00000296595.11	TSL:1 MANE Select	c.108-5908T>G		intron	N/A	ENSP00000296595.6
	TMEM161B	ENST00000510089.5	TSL:1	n.-274-5908T>G		intron	N/A	ENSP00000423380.1
	TMEM161B	ENST00000511087.5	TSL:1	n.108-5908T>G		intron	N/A	ENSP00000421805.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43014 AN: 151972 Hom.: 7316 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.283 AC: 43062 AN: 152090 Hom.: 7326 Cov.: 32 AF XY: 0.281 AC XY: 20897 AN XY: 74354

African (AFR) AF: 0.466 AC: 19310 AN: 41442

American (AMR) AF: 0.198 AC: 3030 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1416 AN: 3468

East Asian (EAS) AF: 0.00387 AC: 20 AN: 5172

South Asian (SAS) AF: 0.341 AC: 1644 AN: 4818

European-Finnish (FIN) AF: 0.177 AC: 1875 AN: 10594

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14855 AN: 67988

Other (OTH) AF: 0.285 AC: 602 AN: 2112

Alfa AF: 0.250 Hom.: 15587

Bravo AF: 0.290

Asia WGS AF: 0.164 AC: 573 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	1.9
DANN	Benign	0.64
PhyloP100		-0.16
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: rs247916; hg19: chr5-87530253;