NM_153354.5:c.600G>T

Variant names:

• chr5-88206498-C-A
• rs183584058
• NM_153354.5:c.600G>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_153354.5(TMEM161B):​c.600G>T​(p.Gly200Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 1,577,322 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00095 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000088 (1 hom.)
• Consequence: TMEM161B NM_153354.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.00004140
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.226
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 5-88206498-C-A is Benign according to our data. Variant chr5-88206498-C-A is described in ClinVar as Benign. ClinVar VariationId is 776050.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.226 with no splicing effect.

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.600G>T	p.Gly200Gly	splice_region synonymous	Exon 7 of 12	NP_699185.1	Q8NDZ6-1
	TMEM161B	NM_001349407.2		c.600G>T	p.Gly200Gly	splice_region synonymous	Exon 7 of 15	NP_001336336.1
	TMEM161B	NM_001289007.2		c.600G>T	p.Gly200Gly	splice_region synonymous	Exon 7 of 13	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.600G>T	p.Gly200Gly	splice_region synonymous	Exon 7 of 12	ENSP00000296595.6	Q8NDZ6-1
	TMEM161B	ENST00000510089.5	TSL:1	n.219G>T		splice_region non_coding_transcript_exon	Exon 6 of 9	ENSP00000423380.1	Q8NDZ6-3
	TMEM161B	ENST00000511087.5	TSL:1	n.*321G>T		splice_region non_coding_transcript_exon	Exon 8 of 13	ENSP00000421805.1	D6RAR3

Frequencies

GnomAD3 genomes AF: 0.000962 AC: 145 AN: 150802 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00341

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000254 AC: 51 AN: 201108 AF XY: 0.000237

Gnomad AFR exome AF: 0.00335

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000111

Gnomad OTH exome AF: 0.000419

GnomAD4 exome AF: 0.0000876 AC: 125 AN: 1426416 Hom.: 1 Cov.: 30 AF XY: 0.0000762 AC XY: 54 AN XY: 708376

African (AFR) AF: 0.00317 AC: 100 AN: 31526

American (AMR) AF: 0.000153 AC: 6 AN: 39316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24982

East Asian (EAS) AF: 0.00 AC: 0 AN: 39270

South Asian (SAS) AF: 0.0000508 AC: 4 AN: 78798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5324

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096404

Other (OTH) AF: 0.000256 AC: 15 AN: 58556

GnomAD4 genome AF: 0.000954 AC: 144 AN: 150906 Hom.: 0 Cov.: 33 AF XY: 0.000869 AC XY: 64 AN XY: 73678

African (AFR) AF: 0.00340 AC: 140 AN: 41142

American (AMR) AF: 0.000197 AC: 3 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67678

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000763 Hom.: 0

Bravo AF: 0.00104

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	-0.41
CADD	Benign	3.8
DANN	Benign	0.65
PhyloP100		-0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000041
dbscSNV1_RF	Benign	0.0040
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: rs183584058; hg19: chr5-87502315;