5-88196456-T-C

Variant names:

• chr5-88196456-T-C
• rs758337035
• NM_153354.5:c.1219A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_153354.5(TMEM161B):​c.1219A>G​(p.Ile407Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,459,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: TMEM161B NM_153354.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.31
• Publications: 0 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02664736).
• BP6: Variant 5-88196456-T-C is Benign according to our data. Variant chr5-88196456-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3178918.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1219A>G	p.Ile407Val	missense	Exon 12 of 12	NP_699185.1	Q8NDZ6-1
	TMEM161B	NM_001349407.2		c.1219A>G	p.Ile407Val	missense	Exon 12 of 15	NP_001336336.1
	TMEM161B	NM_001289007.2		c.1219A>G	p.Ile407Val	missense	Exon 12 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.1219A>G	p.Ile407Val	missense	Exon 12 of 12	ENSP00000296595.6	Q8NDZ6-1
	TMEM161B	ENST00000510089.5	TSL:1	n.*5496A>G		non_coding_transcript_exon	Exon 9 of 9	ENSP00000423380.1	Q8NDZ6-3
	TMEM161B	ENST00000511087.5	TSL:1	n.*953A>G		non_coding_transcript_exon	Exon 13 of 13	ENSP00000421805.1	D6RAR3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000204 AC: 5 AN: 245498 AF XY: 0.00000752

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000294

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000908

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000192 AC: 28 AN: 1459038 Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9 AN XY: 725764

African (AFR) AF: 0.00 AC: 0 AN: 33306

American (AMR) AF: 0.0000225 AC: 1 AN: 44374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25948

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39624

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1110720

Other (OTH) AF: 0.0000166 AC: 1 AN: 60262

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.0020
DANN	Benign	0.41
DEOGEN2	Benign	0.00077	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.90	N
PhyloP100		-1.3
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.022
Sift	Benign	0.72	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.28		Gain of disorder (P = 0.1084)
MVP		0.030
MPC		0.15
ClinPred		0.0075	T
GERP RS		-12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.011
gMVP		0.093
Mutation Taster		=99/1	polymorphism

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: rs758337035; hg19: chr5-87492273;