dbSNP rs148897535: SCMH1:p.Leu556Leu (chr1-41037372-T-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001394311.1(SCMH1):c.1668A>G(p.Leu556Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000471 in 1,614,000 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 1 hom. )

Consequence

SCMH1
NM_001394311.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.28

Publications

2 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: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 1-41037372-T-C is Benign according to our data. Variant chr1-41037372-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2638727.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.28 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394311.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCMH1	NM_001394311.1	MANE Select	c.1668A>G	p.Leu556Leu	synonymous	Exon 13 of 16	NP_001381240.1	A0A8Q3SHN2
SCMH1	NM_001031694.3		c.1638A>G	p.Leu546Leu	synonymous	Exon 15 of 18	NP_001026864.1	Q96GD3-1
SCMH1	NM_001394300.1		c.1638A>G	p.Leu546Leu	synonymous	Exon 16 of 19	NP_001381229.1	Q96GD3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCMH1	ENST00000695335.1	MANE Select	c.1668A>G	p.Leu556Leu	synonymous	Exon 13 of 16	ENSP00000511813.1	A0A8Q3SHN2
SCMH1	ENST00000326197.11	TSL:1	c.1638A>G	p.Leu546Leu	synonymous	Exon 12 of 15	ENSP00000318094.7	Q96GD3-1
SCMH1	ENST00000372595.5	TSL:1	c.1455A>G	p.Leu485Leu	synonymous	Exon 12 of 15	ENSP00000361676.1	Q96GD3-3

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000626

AC:

157

AN:

250818

AF XY:

0.000731

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00478

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000548

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.000481

AC:

703

AN:

1461740

Hom.:

Cov.:

AF XY:

0.000517

AC XY:

376

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33476

American (AMR)

AF:

0.000760

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00501

AC:

131

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000603

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00226

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.000380

AC:

422

AN:

1111944

Other (OTH)

AF:

0.000762

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

103

138

172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000381

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41558

American (AMR)

AF:

0.000589

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000622

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68008

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000605

Hom.:

Bravo

AF:

0.000378

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000830

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

2.6

(source)

DANN

Benign

0.65

PhyloP100

-2.3

PromoterAI

0.043

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over