chr5-88206508-G-A

Variant names:

• chr5-88206508-G-A
• rs357515
• NM_153354.5:c.599-9C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153354.5(TMEM161B):​c.599-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 1,299,246 control chromosomes in the GnomAD database, including 334,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (49666 hom., cov: 30)
  • Exomes 𝑓: 0.73 (284438 hom.)
• Consequence: TMEM161B NM_153354.5 intron
• Scores: Splicing: ADA: 0.00001559
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.364
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-88206508-G-A is Benign according to our data. Variant chr5-88206508-G-A is described in ClinVar as Benign. ClinVar VariationId is 768018.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.852 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.599-9C>T		intron	N/A	NP_699185.1	Q8NDZ6-1
	TMEM161B	NM_001349407.2		c.599-9C>T		intron	N/A	NP_001336336.1
	TMEM161B	NM_001289007.2		c.599-9C>T		intron	N/A	NP_001275936.1	E9PCX5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM161B	ENST00000296595.11	TSL:1 MANE Select	c.599-9C>T		intron	N/A	ENSP00000296595.6	Q8NDZ6-1
	TMEM161B	ENST00000510089.5	TSL:1	n.218-9C>T		intron	N/A	ENSP00000423380.1	Q8NDZ6-3
	TMEM161B	ENST00000511087.5	TSL:1	n.*320-9C>T		intron	N/A	ENSP00000421805.1	D6RAR3

Frequencies

GnomAD3 genomes AF: 0.817 AC: 121911 AN: 149240 Hom.: 49645 Cov.: 30

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.812

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.790

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.825

GnomAD2 exomes AF: 0.699 AC: 109689 AN: 157002 AF XY: 0.699

Gnomad AFR exome AF: 0.657

Gnomad AMR exome AF: 0.707

Gnomad ASJ exome AF: 0.711

Gnomad EAS exome AF: 0.681

Gnomad FIN exome AF: 0.660

Gnomad NFE exome AF: 0.715

Gnomad OTH exome AF: 0.712

GnomAD4 exome AF: 0.733 AC: 843067 AN: 1149922 Hom.: 284438 Cov.: 26 AF XY: 0.731 AC XY: 416533 AN XY: 569838

African (AFR) AF: 0.635 AC: 16377 AN: 25792

American (AMR) AF: 0.684 AC: 19027 AN: 27806

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 14121 AN: 19212

East Asian (EAS) AF: 0.628 AC: 20361 AN: 32438

South Asian (SAS) AF: 0.724 AC: 44955 AN: 62056

European-Finnish (FIN) AF: 0.681 AC: 28805 AN: 42320

Middle Eastern (MID) AF: 0.745 AC: 3118 AN: 4184

European-Non Finnish (NFE) AF: 0.745 AC: 662674 AN: 889330

Other (OTH) AF: 0.719 AC: 33629 AN: 46784

GnomAD4 genome AF: 0.817 AC: 121970 AN: 149324 Hom.: 49666 Cov.: 30 AF XY: 0.816 AC XY: 59409 AN XY: 72832

African (AFR) AF: 0.741 AC: 30176 AN: 40740

American (AMR) AF: 0.825 AC: 12365 AN: 14994

Ashkenazi Jewish (ASJ) AF: 0.881 AC: 3044 AN: 3454

East Asian (EAS) AF: 0.786 AC: 4013 AN: 5108

South Asian (SAS) AF: 0.840 AC: 3992 AN: 4754

European-Finnish (FIN) AF: 0.821 AC: 8100 AN: 9862

Middle Eastern (MID) AF: 0.792 AC: 228 AN: 288

European-Non Finnish (NFE) AF: 0.858 AC: 57623 AN: 67162

Other (OTH) AF: 0.824 AC: 1697 AN: 2060

Alfa AF: 0.836 Hom.: 19097

Bravo AF: 0.806

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.54
DANN	Benign	0.20
PhyloP100		0.36
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.062
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: rs357515; hg19: chr5-87502325; COSMIC: COSV56932472; COSMIC: COSV56932472;