1-108650378-C-A

Position:

• chr1-108650378-C-A

Variant summary

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

The NM_001102592.2(HENMT1):​c.589G>T​(p.Val197Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: HENMT1 NM_001102592.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93

Genes affected

HENMT1 (HGNC:26400): (HEN methyltransferase 1) Enables small RNA 2'-O-methyltransferase. Involved in RNA methylation. Predicted to be located in P granule. Predicted to be active in cytoplasm and nucleus. [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=0.24254483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HENMT1	NM_001102592.2	c.589G>T	p.Val197Leu	missense_variant	7/8	ENST00000651461.1
HENMT1	NM_144584.3	c.589G>T	p.Val197Leu	missense_variant	7/8
HENMT1	XM_005270411.2	c.613G>T	p.Val205Leu	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HENMT1	ENST00000651461.1	c.589G>T	p.Val197Leu	missense_variant	7/8		NM_001102592.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Sep 14, 2022

The c.589G>T (p.V197L) alteration is located in exon 7 (coding exon 6) of the HENMT1 gene. This alteration results from a G to T substitution at nucleotide position 589, causing the valine (V) at amino acid position 197 to be replaced by a leucine (L). 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	Uncertain	0.41
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T;.;T;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.76	T;T;.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;L;.
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.18
Sift	Uncertain	0.019	D;D;D;D
Sift4G	Uncertain	0.052	T;D;T;D
Polyphen		0.99	D;.;D;.
Vest4		0.46
MutPred		0.49		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.19
MPC		0.17
ClinPred		0.77	D
GERP RS		4.5
Varity_R		0.39
gMVP		0.62

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: chr1-109193000;