NM_001378107.1:c.1631A>C

Variant names:

• chr2-135649909-A-C
• rs1446585
• NM_001378107.1:c.1631A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378107.1(R3HDM1):​c.1631A>C​(p.His544Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 6/6 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: R3HDM1 NM_001378107.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.66
• Publications: 48 publications found

Genes affected

R3HDM1 (HGNC:9757): (R3H domain containing 1) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000308733 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378107.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM1	NM_001378107.1	MANE Select	c.1631A>C	p.His544Pro	missense	Exon 17 of 27	NP_001365036.1
	R3HDM1	NM_001282798.2		c.1624-1821A>C		intron	N/A	NP_001269727.1
	R3HDM1	NM_001354200.2		c.1624-1821A>C		intron	N/A	NP_001341129.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM1	ENST00000683871.1	MANE Select	c.1631A>C	p.His544Pro	missense	Exon 17 of 27	ENSP00000506980.1
	R3HDM1	ENST00000264160.8	TSL:1	c.1624-1824A>C		intron	N/A	ENSP00000264160.4
	R3HDM1	ENST00000409478.5	TSL:1	c.1237-1821A>C		intron	N/A	ENSP00000386457.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1109342 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 542284

African (AFR) AF: 0.00 AC: 0 AN: 23164

American (AMR) AF: 0.00 AC: 0 AN: 24246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14628

East Asian (EAS) AF: 0.00 AC: 0 AN: 11644

South Asian (SAS) AF: 0.00 AC: 0 AN: 67174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4232

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 898476

Other (OTH) AF: 0.00 AC: 0 AN: 39692

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 34702

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Benign	0.95
PhyloP100		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs1446585; hg19: chr2-136407479;