chr2-135641568-A-G

Position:

• chr2-135641568-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378107.1(R3HDM1):​c.1252A>G​(p.Thr418Ala) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: R3HDM1 NM_001378107.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.68

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24131274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
R3HDM1	NM_001378107.1	c.1252A>G	p.Thr418Ala	missense_variant	15/27	ENST00000683871.1	NP_001365036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
R3HDM1	ENST00000683871.1	c.1252A>G	p.Thr418Ala	missense_variant	15/27		NM_001378107.1	ENSP00000506980	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 27, 2022

The c.1252A>G (p.T418A) alteration is located in exon 15 (coding exon 13) of the R3HDM1 gene. This alteration results from a A to G substitution at nucleotide position 1252, causing the threonine (T) at amino acid position 418 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.0054	T;.;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.5	L;.;L
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.37	N;N;N
REVEL	Benign	0.10
Sift	Benign	0.35	T;T;T
Sift4G	Benign	0.73	T;T;T
Polyphen		0.83	P;.;.
Vest4		0.49
MutPred		0.28		Loss of glycosylation at S417 (P = 0.0955);.;Loss of glycosylation at S417 (P = 0.0955);
MVP		0.54
MPC		0.26
ClinPred		0.53	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-136399138;