NM_001394311.1:c.13+10466A>G

Variant names:

• chr1-41175655-T-C
• rs6656085
• NM_001394311.1:c.13+10466A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394311.1(SCMH1):​c.13+10466A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,022 control chromosomes in the GnomAD database, including 18,079 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 0.46 (18079 hom., cov: 31)
• Consequence: SCMH1 NM_001394311.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCMH1	NM_001394311.1	MANE Select	c.13+10466A>G		intron	N/A	NP_001381240.1
	SCMH1	NM_001031694.3		c.-370+10466A>G		intron	N/A	NP_001026864.1
	SCMH1	NM_001394300.1		c.-571+10466A>G		intron	N/A	NP_001381229.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCMH1	ENST00000695335.1	MANE Select	c.13+10466A>G		intron	N/A	ENSP00000511813.1
	SCMH1	ENST00000372597.5	TSL:1	c.-297+10466A>G		intron	N/A	ENSP00000361678.1
	SCMH1	ENST00000372596.5	TSL:1	c.-410+10466A>G		intron	N/A	ENSP00000361677.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70406 AN: 151900 Hom.: 18068 Cov.: 31

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.463 AC: 70458 AN: 152022 Hom.: 18079 Cov.: 31 AF XY: 0.467 AC XY: 34688 AN XY: 74318

African (AFR) AF: 0.226 AC: 9381 AN: 41456

American (AMR) AF: 0.598 AC: 9137 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1884 AN: 3462

East Asian (EAS) AF: 0.548 AC: 2832 AN: 5170

South Asian (SAS) AF: 0.517 AC: 2490 AN: 4816

European-Finnish (FIN) AF: 0.525 AC: 5551 AN: 10572

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37531 AN: 67958

Other (OTH) AF: 0.504 AC: 1065 AN: 2112

Alfa AF: 0.458 Hom.: 2610

Bravo AF: 0.460

Asia WGS AF: 0.501 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.68
PhyloP100		-0.072
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6656085; hg19: chr1-41641327;