rs112634290

Variant names:

• chr20-44343480-G-A
• rs112634290
• NM_178491.4:c.484G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-44343480-G-A
• chr20-44343480-G-C
• chr20-44343480-G-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.484G>A​(p.Asp162Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000314 in 1,611,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: R3HDML NM_178491.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.246
• Publications: 1 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 (MetaRNN=0.048400044).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178491.4. 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
	R3HDML	NM_178491.4	MANE Select	c.484G>A	p.Asp162Asn	missense	Exon 3 of 5	NP_848586.1	Q9H3Y0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDML	ENST00000217043.4	TSL:1 MANE Select	c.484G>A	p.Asp162Asn	missense	Exon 3 of 5	ENSP00000217043.3	Q9H3Y0
	R3HDML-AS1	ENST00000735551.1		n.601-4420C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 152134 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000382

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000205 AC: 51 AN: 248918 AF XY: 0.000245

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.000207

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000301

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000316 AC: 461 AN: 1459600 Hom.: 0 Cov.: 31 AF XY: 0.000302 AC XY: 219 AN XY: 726052

African (AFR) AF: 0.000449 AC: 15 AN: 33398

American (AMR) AF: 0.000315 AC: 14 AN: 44392

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26060

East Asian (EAS) AF: 0.00 AC: 0 AN: 39504

South Asian (SAS) AF: 0.0000699 AC: 6 AN: 85786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.000375 AC: 417 AN: 1111000

Other (OTH) AF: 0.000149 AC: 9 AN: 60304

GnomAD4 genome AF: 0.000296 AC: 45 AN: 152134 Hom.: 0 Cov.: 32 AF XY: 0.000283 AC XY: 21 AN XY: 74312

African (AFR) AF: 0.000410 AC: 17 AN: 41436

American (AMR) AF: 0.000131 AC: 2 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

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: 316

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000261

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000239 AC: 29

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000357

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.83
DEOGEN2	Benign	0.00031	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.82	N
PhyloP100		0.25
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.021
Sift	Benign	0.12	T
Sift4G	Benign	0.30	T
Polyphen		0.0020	B
Vest4		0.20
MVP		0.085
MPC		0.13
ClinPred		0.0079	T
GERP RS		1.4
Varity_R		0.030
gMVP		0.55
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs112634290; hg19: chr20-42972120;