dbSNP rs780713552: SCMH1:p.Glu630Gly (chr1-41028318-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001394311.1(SCMH1):c.1889A>G(p.Glu630Gly) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,388,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

SCMH1
NM_001394311.1 missense, splice_region

Scores

Splicing: ADA: 0.8891

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.838

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCMH1	NM_001394311.1 link	c.1889A>G	p.Glu630Gly	missense_variant, splice_region_variant	Exon 16 of 16	ENST00000695335.1	NP_001381240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCMH1	ENST00000695335.1 link	c.1889A>G	p.Glu630Gly	missense_variant, splice_region_variant	Exon 16 of 16		NM_001394311.1	ENSP00000511813.1		A0A8Q3SHN2

Frequencies

GnomAD3 genomes

AF:

0.0000731

AC:

AN:

150516

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000399

AC:

AN:

250574

AF XY:

0.0000517

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000193

AC:

239

AN:

1238024

Hom.:

Cov.:

AF XY:

0.000178

AC XY:

111

AN XY:

624356

show subpopulations

African (AFR)

AF:

0.0000347

AC:

AN:

28858

American (AMR)

AF:

0.0000230

AC:

AN:

43496

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23804

East Asian (EAS)

AF:

0.00

AC:

AN:

35534

South Asian (SAS)

AF:

0.00

AC:

AN:

81990

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5226

European-Non Finnish (NFE)

AF:

0.000249

AC:

229

AN:

921150

Other (OTH)

AF:

0.000155

AC:

AN:

51724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.569

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000731

AC:

AN:

150516

Hom.:

Cov.:

AF XY:

0.0000816

AC XY:

AN XY:

73490

show subpopulations

African (AFR)

AF:

0.0000486

AC:

AN:

41162

American (AMR)

AF:

0.00

AC:

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5060

South Asian (SAS)

AF:

0.00

AC:

AN:

4680

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000133

AC:

AN:

67554

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 02, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1859A>G (p.E620G) alteration is located in exon 16 (coding exon 13) of the SCMH1 gene. This alteration results from a A to G substitution at nucleotide position 1859, causing the glutamic acid (E) at amino acid position 620 to be replaced by a glycine (G). 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

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.61

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

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.84

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

M_CAP

Benign

0.085

MetaRNN

Pathogenic

0.84

D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.32

MutationAssessor

Uncertain

2.5

M;.;.;.;.;M;.;.;.;.;.;.

PhyloP100

7.7

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-6.1

.;.;D;D;D;D;D;D;D;D;.;D

REVEL

Uncertain

0.55

Sift

Uncertain

0.0010

.;.;D;D;D;D;D;D;D;D;.;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

0.93

P;.;.;.;P;P;.;D;P;.;.;.

Vest4

0.76

MVP

0.67

MPC

1.1

ClinPred

0.93

GERP RS

5.0

Varity_R

0.67

gMVP

0.70

Mutation Taster

=55/45

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.89

dbscSNV1_RF

Benign

0.72

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

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rs780713552

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over