1-41037372-T-C

Variant names:

• chr1-41037372-T-C
• rs148897535
• NM_001394311.1:c.1668A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.28
• Publications: 2 publications found

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]

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

ACMG classification

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 id is 2638727.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.28 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCMH1	NM_001394311.1	c.1668A>G	p.Leu556Leu	synonymous_variant	Exon 13 of 16	ENST00000695335.1	NP_001381240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCMH1	ENST00000695335.1	c.1668A>G	p.Leu556Leu	synonymous_variant	Exon 13 of 16		NM_001394311.1	ENSP00000511813.1

Frequencies

GnomAD3 genomes AF: 0.000381 AC: 58 AN: 152142 Hom.: 0 Cov.: 32

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

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.: 1 Cov.: 31 AF XY: 0.000517 AC XY: 376 AN XY: 727172

African (AFR) AF: 0.000119 AC: 4 AN: 33476

American (AMR) AF: 0.000760 AC: 34 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00501 AC: 131 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000603 AC: 52 AN: 86244

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53408

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5742

European-Non Finnish (NFE) AF: 0.000380 AC: 422 AN: 1111944

Other (OTH) AF: 0.000762 AC: 46 AN: 60388

GnomAD4 genome AF: 0.000381 AC: 58 AN: 152260 Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30 AN XY: 74442

African (AFR) AF: 0.0000481 AC: 2 AN: 41558

American (AMR) AF: 0.000589 AC: 9 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68008

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000605 Hom.: 0

Bravo AF: 0.000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000830

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SCMH1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.6
DANN	Benign	0.65
PhyloP100		-2.3
PromoterAI		0.043	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs148897535; hg19: chr1-41503044;