19-55312964-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. L199V) has been classified as Uncertain significance.

• 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
• Publications: 49 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282011.2. 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
	TMEM150B	NM_001282011.2	MANE Select	c.597A>C	p.Leu199Phe	missense	Exon 8 of 8	NP_001268940.1
	TMEM150B	NM_001085488.3		c.597A>C	p.Leu199Phe	missense	Exon 8 of 8	NP_001078957.1
	TMEM150B	NR_104066.2		n.752A>C		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM150B	ENST00000326652.9	TSL:1 MANE Select	c.597A>C	p.Leu199Phe	missense	Exon 8 of 8	ENSP00000320757.4
	TMEM150B	ENST00000586609.5	TSL:1	n.*337A>C		non_coding_transcript_exon	Exon 7 of 7	ENSP00000466957.1
	TMEM150B	ENST00000592603.5	TSL:1	n.*337A>C		non_coding_transcript_exon	Exon 7 of 7	ENSP00000468745.1

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

GnomAD2 exomes AF: 0.515 AC: 127193 AN: 247162 AF XY: 0.516

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 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

African (AFR) AF: 0.924 AC: 30931 AN: 33466

American (AMR) AF: 0.491 AC: 21902 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 15399 AN: 26108

East Asian (EAS) AF: 0.188 AC: 7451 AN: 39662

South Asian (SAS) AF: 0.585 AC: 50461 AN: 86202

European-Finnish (FIN) AF: 0.452 AC: 24083 AN: 53272

Middle Eastern (MID) AF: 0.541 AC: 3006 AN: 5560

European-Non Finnish (NFE) AF: 0.508 AC: 564214 AN: 1111626

Other (OTH) AF: 0.527 AC: 31800 AN: 60328

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

African (AFR) AF: 0.907 AC: 37691 AN: 41558

American (AMR) AF: 0.543 AC: 8306 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2077 AN: 3472

East Asian (EAS) AF: 0.171 AC: 882 AN: 5172

South Asian (SAS) AF: 0.580 AC: 2797 AN: 4826

European-Finnish (FIN) AF: 0.458 AC: 4836 AN: 10566

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34406 AN: 67962

Other (OTH) AF: 0.608 AC: 1284 AN: 2112

Alfa AF: 0.526 Hom.: 93856

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 v4.9

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
PhyloP100		-3.9
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
Mutation Taster		=98/2	polymorphism (auto)

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