rs6686842

Positions:

• chr1-41065199-T-C
• chr1-41065199-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394311.1(SCMH1):​c.1105+5396A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,020 control chromosomes in the GnomAD database, including 32,780 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (32780 hom., cov: 31)
• Consequence: SCMH1 NM_001394311.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCMH1	NM_001394311.1	c.1105+5396A>G		intron_variant		ENST00000695335.1	NP_001381240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCMH1	ENST00000695335.1	c.1105+5396A>G		intron_variant			NM_001394311.1	ENSP00000511813	A2

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97637 AN: 151902 Hom.: 32727 Cov.: 31

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.621

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.643 AC: 97746 AN: 152020 Hom.: 32780 Cov.: 31 AF XY: 0.638 AC XY: 47376 AN XY: 74306

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.623

Alfa AF: 0.579 Hom.: 34808

Bravo AF: 0.642

Asia WGS AF: 0.660 AC: 2299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.65

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

LitVar

Other links and lift over

dbSNP: rs6686842; hg19: chr1-41530871; COSMIC: COSV58233567;