rs780195099

Variant names:

• chr1-41028206-C-G
• rs780195099
• NM_001394311.1:c.2001G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-41028206-C-G
• chr1-41028206-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001394311.1(SCMH1):​c.2001G>C​(p.Gln667His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: SCMH1 NM_001394311.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.368822).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCMH1	NM_001394311.1	MANE Select	c.2001G>C	p.Gln667His	missense	Exon 16 of 16	NP_001381240.1	A0A8Q3SHN2
	SCMH1	NM_001031694.3		c.1971G>C	p.Gln657His	missense	Exon 18 of 18	NP_001026864.1	Q96GD3-1
	SCMH1	NM_001394300.1		c.1971G>C	p.Gln657His	missense	Exon 19 of 19	NP_001381229.1	Q96GD3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCMH1	ENST00000695335.1	MANE Select	c.2001G>C	p.Gln667His	missense	Exon 16 of 16	ENSP00000511813.1	A0A8Q3SHN2
	SCMH1	ENST00000326197.11	TSL:1	c.1971G>C	p.Gln657His	missense	Exon 15 of 15	ENSP00000318094.7	Q96GD3-1
	SCMH1	ENST00000372595.5	TSL:1	c.1788G>C	p.Gln596His	missense	Exon 15 of 15	ENSP00000361676.1	Q96GD3-3

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 251170 AF XY: 0.0000147

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: 0.0000617

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000465 AC: 68 AN: 1461852 Hom.: 0 Cov.: 34 AF XY: 0.0000358 AC XY: 26 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000594 AC: 66 AN: 1111990

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152196 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74352

African (AFR) AF: 0.0000241 AC: 1 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000450 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.2
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.16
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.014	D
Polyphen		0.46	P
Vest4		0.28
MutPred		0.58		Gain of methylation at R654 (P = 0.0854)
MVP		0.48
MPC		0.98
ClinPred		0.49	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.11
gMVP		0.25
Mutation Taster		=71/29	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: rs780195099; hg19: chr1-41493878;