chr7-141212691-G-C

Position:

• chr7-141212691-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001195278.2(TMEM178B):​c.483G>C​(p.Glu161Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000145 in 1,383,530 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TMEM178B NM_001195278.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.96

Genes affected

TMEM178B (HGNC:44112): (transmembrane protein 178B) Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM178B	NM_001195278.2	c.483G>C	p.Glu161Asp	missense_variant	2/4	ENST00000565468.6
TMEM178B	XM_011515705.3	c.483G>C	p.Glu161Asp	missense_variant	2/4
TMEM178B	XM_017011636.2	c.483G>C	p.Glu161Asp	missense_variant	2/4
TMEM178B	XR_001744505.2	n.730G>C		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM178B	ENST00000565468.6	c.483G>C	p.Glu161Asp	missense_variant	2/4	5	NM_001195278.2	P1
TMEM178B	ENST00000563442.1	n.401G>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1383530 Hom.: 0 Cov.: 30 AF XY: 0.00000293 AC XY: 2 AN XY: 682744

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.483G>C (p.E161D) alteration is located in exon 2 (coding exon 2) of the TMEM178B gene. This alteration results from a G to C substitution at nucleotide position 483, causing the glutamic acid (E) at amino acid position 161 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.60	D
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	0.99	D
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.9	N
Sift	Benign	0.047	D
Sift4G	Benign	0.070	T
Vest4		0.68
MVP		0.62
GERP RS		4.8
Varity_R		0.22
gMVP		0.83

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-140912491;