chr20-44341221-C-T

Variant names:

• chr20-44341221-C-T
• NM_178491.4:c.287C>T

Variant summary

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

The NM_178491.4(R3HDML):​c.287C>T​(p.Ala96Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: R3HDML NM_178491.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.48

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]

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=0.2312361).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
R3HDML	NM_178491.4	c.287C>T	p.Ala96Val	missense_variant	Exon 2 of 5	ENST00000217043.4	NP_848586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
R3HDML	ENST00000217043.4	c.287C>T	p.Ala96Val	missense_variant	Exon 2 of 5	1	NM_178491.4	ENSP00000217043.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461472 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726976

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.29	N
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.10
Sift	Benign	0.058	T
Sift4G	Benign	0.29	T
Polyphen		0.0070	B
Vest4		0.12
MutPred		0.62		Gain of catalytic residue at A96 (P = 0.0766);
MVP		0.14
MPC		0.14
ClinPred		0.39	T
GERP RS		4.6
Varity_R		0.13
gMVP		0.66

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-42969861;