4-38988868-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024943.3(TMEM156):c.722G>A(p.Arg241Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM156 NM_024943.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.269

Genes affected

TMEM156 (HGNC:26260): (transmembrane protein 156) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06353694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM156	NM_024943.3	c.722G>A	p.Arg241Lys	missense_variant	4/7	ENST00000381938.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM156	ENST00000381938.4	c.722G>A	p.Arg241Lys	missense_variant	4/7	1	NM_024943.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Apr 07, 2022

The c.722G>A (p.R241K) alteration is located in exon 4 (coding exon 4) of the TMEM156 gene. This alteration results from a G to A substitution at nucleotide position 722, causing the arginine (R) at amino acid position 241 to be replaced by a lysine (K). 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	Benign	0.097
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	14
Dann	Benign	0.97
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.033
Sift	Benign	0.20	T
Sift4G	Benign	0.48	T
Polyphen		0.060	B
Vest4		0.10
MutPred		0.31		Gain of methylation at R241 (P = 0.0033);
MVP		0.25
MPC		0.047
ClinPred		0.25	T
GERP RS		1.3
Varity_R		0.039
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr4-38990488;