1-41037482-T-A

Variant names:

• chr1-41037482-T-A
• rs561244725
• NM_001394311.1:c.1558A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394311.1(SCMH1):​c.1558A>T​(p.Met520Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M520V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCMH1 NM_001394311.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.51
• 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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18556398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCMH1	NM_001394311.1	c.1558A>T	p.Met520Leu	missense_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.1558A>T	p.Met520Leu	missense_variant	Exon 13 of 16		NM_001394311.1	ENSP00000511813.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.11	T;.;.;.;.;T;.;.;.;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.016
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.82	T;T;.;D;D;.;.;D;.;.;D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;.;.;.;L;.;.;.;.;.
PhyloP100		3.5
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.1	.;.;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.19	.;.;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.58	T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0080	B;.;.;.;B;B;.;B;B;.;.
Vest4		0.40
MutPred		0.096		Gain of glycosylation at S509 (P = 0.1242);.;.;.;.;Gain of glycosylation at S509 (P = 0.1242);.;.;.;.;.;
MVP		0.63
MPC		0.28
ClinPred		0.58	D
GERP RS		4.3
PromoterAI		0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.23
Mutation Taster		=85/15	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: rs561244725; hg19: chr1-41503154;