1-41048720-T-G

Variant names:

• chr1-41048720-T-G
• NM_001394311.1:c.1276A>C

Variant summary

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

The NM_001394311.1(SCMH1):​c.1276A>C​(p.Lys426Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCMH1 NM_001394311.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.65
• Publications: 0 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: 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=0.27443296).

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.1276A>C	p.Lys426Gln	missense	Exon 11 of 16	NP_001381240.1	A0A8Q3SHN2
	SCMH1	NM_001031694.3		c.1246A>C	p.Lys416Gln	missense	Exon 13 of 18	NP_001026864.1	Q96GD3-1
	SCMH1	NM_001394300.1		c.1246A>C	p.Lys416Gln	missense	Exon 14 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.1276A>C	p.Lys426Gln	missense	Exon 11 of 16	ENSP00000511813.1	A0A8Q3SHN2
	SCMH1	ENST00000326197.11	TSL:1	c.1246A>C	p.Lys416Gln	missense	Exon 10 of 15	ENSP00000318094.7	Q96GD3-1
	SCMH1	ENST00000372595.5	TSL:1	c.1063A>C	p.Lys355Gln	missense	Exon 10 of 15	ENSP00000361676.1	Q96GD3-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.33
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.16
Sift	Benign	0.12	T
Sift4G	Benign	0.18	T
Polyphen		0.68	P
Vest4		0.42
MutPred		0.35		Loss of ubiquitination at K416 (P = 0.0283)
MVP		0.43
MPC		0.68
ClinPred		0.90	D
GERP RS		6.1
Varity_R		0.20
gMVP		0.60
Mutation Taster		=92/8	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

hg19: chr1-41514392;