NM_001037540.3:c.536C>T

Variant names:

• chrX-17750126-C-T
• NM_001037540.3:c.536C>T

Variant summary

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

The NM_001037540.3(SCML1):​c.536C>T​(p.Pro179Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,021 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: SCML1 NM_001037540.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.379
• Publications: 0 publications found

Genes affected

SCML1 (HGNC:10580): (Scm polycomb group protein like 1) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.07456413).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037540.3. 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
	SCML1	NM_001037540.3	MANE Select	c.536C>T	p.Pro179Leu	missense	Exon 6 of 8	NP_001032629.1	Q9UN30-3
	SCML1	NM_006746.6		c.455C>T	p.Pro152Leu	missense	Exon 5 of 7	NP_006737.2	Q9UN30-2
	SCML1	NM_001037535.3		c.173C>T	p.Pro58Leu	missense	Exon 4 of 6	NP_001032624.1	Q9UN30-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCML1	ENST00000380041.8	TSL:5 MANE Select	c.536C>T	p.Pro179Leu	missense	Exon 6 of 8	ENSP00000369380.3	Q9UN30-3
	SCML1	ENST00000380043.7	TSL:1	c.455C>T	p.Pro152Leu	missense	Exon 5 of 7	ENSP00000369382.3	Q9UN30-2
	SCML1	ENST00000380045.7	TSL:1	c.173C>T	p.Pro58Leu	missense	Exon 4 of 6	ENSP00000369384.3	Q9UN30-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098021 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363375

African (AFR) AF: 0.00 AC: 0 AN: 26397

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54141

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40525

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841933

Other (OTH) AF: 0.00 AC: 0 AN: 46094

GnomAD4 genome Cov.: 23

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	0.11
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.7
DANN	Benign	0.90
DEOGEN2	Benign	0.18	T
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.38
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.0070
Sift	Benign	0.042	D
Sift4G	Benign	0.33	T
Polyphen		0.0020	B
Vest4		0.048
MutPred		0.32		Gain of catalytic residue at P179 (P = 0.0457)
MVP		0.043
MPC		0.97
ClinPred		0.079	T
GERP RS		-5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.043
gMVP		0.12
Mutation Taster		=97/3	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: chrX-17768246;