19-55312964-T-G

Variant names:

• chr19-55312964-T-G
• rs7246479
• NM_001282011.2:c.597A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282011.2(TMEM150B):​c.597A>C​(p.Leu199Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,613,016 control chromosomes in the GnomAD database, including 229,682 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.61 (31401 hom., cov: 34)
  • Exomes 𝑓: 0.51 (198281 hom.)
• Consequence: TMEM150B NM_001282011.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.93

Genes affected

TMEM150B (HGNC:34415): (transmembrane protein 150B) This gene encodes a protein that belongs to the DRAM (damage-regulated autophagy modulator) family of membrane-spanning proteins. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.8999013E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM150B	NM_001282011.2	c.597A>C	p.Leu199Phe	missense_variant	Exon 8 of 8	ENST00000326652.9	NP_001268940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM150B	ENST00000326652.9	c.597A>C	p.Leu199Phe	missense_variant	Exon 8 of 8	1	NM_001282011.2	ENSP00000320757.4

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92701 AN: 152046 Hom.: 31332 Cov.: 34

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.604

GnomAD3 exomes AF: 0.515 AC: 127193 AN: 247162 Hom.: 35275 AF XY: 0.516 AC XY: 69312 AN XY: 134436

Gnomad AFR exome AF: 0.923

Gnomad AMR exome AF: 0.484

Gnomad ASJ exome AF: 0.597

Gnomad EAS exome AF: 0.177

Gnomad SAS exome AF: 0.591

Gnomad FIN exome AF: 0.455

Gnomad NFE exome AF: 0.505

Gnomad OTH exome AF: 0.526

GnomAD4 exome AF: 0.513 AC: 749247 AN: 1460852 Hom.: 198281 Cov.: 64 AF XY: 0.515 AC XY: 373914 AN XY: 726704

Gnomad4 AFR exome AF: 0.924

Gnomad4 AMR exome AF: 0.491

Gnomad4 ASJ exome AF: 0.590

Gnomad4 EAS exome AF: 0.188

Gnomad4 SAS exome AF: 0.585

Gnomad4 FIN exome AF: 0.452

Gnomad4 NFE exome AF: 0.508

Gnomad4 OTH exome AF: 0.527

GnomAD4 genome AF: 0.610 AC: 92834 AN: 152164 Hom.: 31401 Cov.: 34 AF XY: 0.602 AC XY: 44803 AN XY: 74364

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.608

Alfa AF: 0.509 Hom.: 39801

Bravo AF: 0.626

TwinsUK AF: 0.507 AC: 1881

ALSPAC AF: 0.513 AC: 1979

ESP6500AA AF: 0.903 AC: 3912

ESP6500EA AF: 0.516 AC: 4404

ExAC AF: 0.521 AC: 63017

Asia WGS AF: 0.479 AC: 1669 AN: 3478

EpiCase AF: 0.516

EpiControl AF: 0.510

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.0010
DANN	Benign	0.58
DEOGEN2	Benign	0.19	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.0081	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	8.9e-7	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-1.2	N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	4.2	N
REVEL	Benign	0.040
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.064
MutPred		0.53		Loss of loop (P = 0.0203);
MPC		0.11
ClinPred		0.026	T
GERP RS		-9.1
Varity_R		0.042
gMVP		0.50

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

LitVar

Other links and lift over

dbSNP: rs7246479; hg19: chr19-55824332; COSMIC: COSV58593519; COSMIC: COSV58593519;