chr19-41383843-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001098821.2(TMEM91):​c.489T>A​(p.Ala163Ala) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM91 NM_001098821.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 32 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=-1.22 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098821.2. 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
	TMEM91	NM_001098821.2	MANE Select	c.489T>A	p.Ala163Ala	synonymous	Exon 4 of 4	NP_001092291.1	Q6ZNR0-1
	TMEM91	NM_001042595.3		c.*223T>A		3_prime_UTR	Exon 4 of 4	NP_001036060.1	Q6ZNR0-2
	TMEM91	NM_001369862.1		c.*13-31T>A		intron	N/A	NP_001356791.1	Q6ZNR0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM91	ENST00000392002.7	TSL:2 MANE Select	c.489T>A	p.Ala163Ala	synonymous	Exon 4 of 4	ENSP00000375859.1	Q6ZNR0-1
	TMEM91	ENST00000356385.8	TSL:1	c.*223T>A		3_prime_UTR	Exon 4 of 4	ENSP00000348750.4	Q6ZNR0-2
	TMEM91	ENST00000539627.5	TSL:1	c.*883T>A		3_prime_UTR	Exon 3 of 3	ENSP00000441900.1	F5GWC9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1455332 Hom.: 0 Cov.: 68 AF XY: 0.00 AC XY: 0 AN XY: 723952

African (AFR) AF: 0.00 AC: 0 AN: 32920

American (AMR) AF: 0.00 AC: 0 AN: 43962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25944

East Asian (EAS) AF: 0.00 AC: 0 AN: 38930

South Asian (SAS) AF: 0.00 AC: 0 AN: 85376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109020

Other (OTH) AF: 0.00 AC: 0 AN: 60104

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.7
DANN	Benign	0.87
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs12602; hg19: chr19-41889748;