19-41383843-T-C

Variant names:

• chr19-41383843-T-C
• rs12602
• NM_001098821.2:c.489T>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001098821.2(TMEM91):​c.489T>C​(p.Ala163Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 1,606,854 control chromosomes in the GnomAD database, including 309,185 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.66 (34346 hom., cov: 31)
  • Exomes 𝑓: 0.61 (274839 hom.)
• Consequence: TMEM91 NM_001098821.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

Genes affected

TMEM91 (HGNC:32393): (transmembrane protein 91) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle and membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255730 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-1.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM91	NM_001098821.2	c.489T>C	p.Ala163Ala	synonymous_variant	Exon 4 of 4	ENST00000392002.7	NP_001092291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM91	ENST00000392002.7	c.489T>C	p.Ala163Ala	synonymous_variant	Exon 4 of 4	2	NM_001098821.2	ENSP00000375859.1
ENSG00000255730	ENST00000540732.3	c.210+5324T>C		intron_variant	Intron 2 of 9	2		ENSP00000443246.1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100393 AN: 151896 Hom.: 34298 Cov.: 31

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.634

GnomAD3 exomes AF: 0.595 AC: 143494 AN: 241300 Hom.: 43821 AF XY: 0.595 AC XY: 78212 AN XY: 131460

Gnomad AFR exome AF: 0.839

Gnomad AMR exome AF: 0.476

Gnomad ASJ exome AF: 0.617

Gnomad EAS exome AF: 0.428

Gnomad SAS exome AF: 0.589

Gnomad FIN exome AF: 0.657

Gnomad NFE exome AF: 0.610

Gnomad OTH exome AF: 0.608

GnomAD4 exome AF: 0.612 AC: 890115 AN: 1454840 Hom.: 274839 Cov.: 68 AF XY: 0.611 AC XY: 441845 AN XY: 723646

Gnomad4 AFR exome AF: 0.842

Gnomad4 AMR exome AF: 0.481

Gnomad4 ASJ exome AF: 0.613

Gnomad4 EAS exome AF: 0.458

Gnomad4 SAS exome AF: 0.584

Gnomad4 FIN exome AF: 0.656

Gnomad4 NFE exome AF: 0.615

Gnomad4 OTH exome AF: 0.618

GnomAD4 genome AF: 0.661 AC: 100496 AN: 152014 Hom.: 34346 Cov.: 31 AF XY: 0.658 AC XY: 48914 AN XY: 74306

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.634

Alfa AF: 0.629 Hom.: 19866

Bravo AF: 0.662

Asia WGS AF: 0.536 AC: 1864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.3
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs12602; hg19: chr19-41889748; COSMIC: COSV55370513; COSMIC: COSV55370513;