chr1-41037509-G-C

Variant names:

• chr1-41037509-G-C
• rs564084016
• NM_001394311.1:c.1531C>G

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.1531C>G​(p.Arg511Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R511C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SCMH1 NM_001394311.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• 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=0.08426222).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCMH1	NM_001394311.1	c.1531C>G	p.Arg511Gly	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.1531C>G	p.Arg511Gly	missense_variant	Exon 13 of 16		NM_001394311.1	ENSP00000511813.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461876 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727240

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

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

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: 0.00000270 AC: 3 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000298 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.075	T;.;.;.;.;T;.;.;.;.;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.81	T;T;.;T;T;.;.;T;.;.;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.084	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	N;.;.;.;.;N;.;.;.;.;.
PhyloP100		2.1
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.45	.;.;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.025
Sift	Benign	0.35	.;.;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.41	T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0	B;.;.;.;B;B;.;B;B;.;.
Vest4		0.16
MutPred		0.23		Gain of catalytic residue at A500 (P = 0.045);.;.;.;.;Gain of catalytic residue at A500 (P = 0.045);.;.;.;.;.;
MVP		0.13
MPC		0.38
ClinPred		0.25	T
GERP RS		2.4
PromoterAI		-0.0043	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.088
gMVP		0.36
Mutation Taster		=84/16	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: rs564084016; hg19: chr1-41503181; COSMIC: COSV106058436; COSMIC: COSV106058436;