Variant 1-41028707-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001394311.1(SCMH1):c.1764G>T(p.Glu588Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SCMH1
NM_001394311.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.301

Variant links:

Genes affected

SCMH1 (HGNC:19003): (Scm polycomb group protein homolog 1) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to act upstream of or within anterior/posterior pattern specification; chromatin remodeling; and spermatogenesis. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SCMH1 links:

SLFNL1-AS1 (HGNC:44126): (SLFNL1 antisense RNA 1)

SLFNL1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0413889).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCMH1	NM_001394311.1 linkuse as main transcript	c.1764G>T	p.Glu588Asp	missense_variant	15/16	ENST00000695335.1
SLFNL1-AS1	NR_037868.1 linkuse as main transcript	n.3987C>A		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCMH1	ENST00000695335.1 linkuse as main transcript	c.1764G>T	p.Glu588Asp	missense_variant	15/16		NM_001394311.1	A2
SLFNL1-AS1	ENST00000626479.1 linkuse as main transcript	n.3987C>A		non_coding_transcript_exon_variant	2/4	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727214

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2024

The c.1734G>T (p.E578D) alteration is located in exon 15 (coding exon 12) of the SCMH1 gene. This alteration results from a G to T substitution at nucleotide position 1734, causing the glutamic acid (E) at amino acid position 578 to be replaced by an aspartic acid (D). 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

0.079

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

Cadd

Benign

Dann

Benign

0.88

DEOGEN2

Benign

0.086

T;.;.;.;.;T;.;.;.;.;T;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.19

LIST_S2

Uncertain

0.92

D;D;.;T;T;.;.;T;.;.;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.041

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.;.;.;.;L;.;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.4

N;.;N;N;N;N;N;N;N;N;.;N

REVEL

Benign

0.051

Sift

Uncertain

0.0030

D;.;T;T;T;T;T;T;T;T;.;T

Sift4G

Benign

0.51

T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0020

B;.;.;.;B;B;.;B;B;.;.;.

Vest4

0.15

MutPred

0.085

Loss of MoRF binding (P = 0.1379);.;.;.;.;Loss of MoRF binding (P = 0.1379);.;.;.;.;.;.;

MVP

0.25

MPC

0.29

ClinPred

0.067

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.028

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over