20-44341158-A-T

Variant names:

• chr20-44341158-A-T
• rs3761184
• NM_178491.4:c.262-38A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_178491.4(R3HDML):​c.262-38A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000227 in 1,538,552 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: R3HDML NM_178491.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 14 publications found

Genes affected

R3HDML (HGNC:16249): (R3H domain containing like) Predicted to enable peptidase inhibitor activity. Predicted to be involved in negative regulation of peptidase activity. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

R3HDML-AS1 (HGNC:55830): (R3HDML antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
R3HDML	NM_178491.4	c.262-38A>T		intron_variant	Intron 1 of 4	ENST00000217043.4	NP_848586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
R3HDML	ENST00000217043.4	c.262-38A>T		intron_variant	Intron 1 of 4	1	NM_178491.4	ENSP00000217043.3
R3HDML-AS1	ENST00000735551.1	n.601-2098T>A		intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152134 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000251 AC: 6 AN: 239062 AF XY: 0.0000155

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000101 AC: 14 AN: 1386300 Hom.: 0 Cov.: 21 AF XY: 0.00000871 AC XY: 6 AN XY: 689008

African (AFR) AF: 0.000219 AC: 7 AN: 32028

American (AMR) AF: 0.00 AC: 0 AN: 42524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24626

East Asian (EAS) AF: 0.00 AC: 0 AN: 38952

South Asian (SAS) AF: 0.00 AC: 0 AN: 82914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5158

European-Non Finnish (NFE) AF: 0.00000476 AC: 5 AN: 1049770

Other (OTH) AF: 0.0000348 AC: 2 AN: 57504

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152252 Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8 AN XY: 74438

African (AFR) AF: 0.000457 AC: 19 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.00 Hom.: 1137

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.53
PhyloP100		-1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3761184; hg19: chr20-42969798;