NM_198081.5:c.-60+5760G>A

Variant names:

• chr6-107818366-C-T
• rs17068819
• NM_198081.5:c.-60+5760G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198081.5(SCML4):​c.-60+5760G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0853 in 152,154 control chromosomes in the GnomAD database, including 585 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.085 (585 hom., cov: 33)
• Consequence: SCML4 NM_198081.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• Publications: 2 publications found

Genes affected

SCML4 (HGNC:21397): (Scm polycomb group protein like 4) 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]

ENSG00000304634 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCML4	NM_198081.5	c.-60+5760G>A		intron_variant	Intron 1 of 7	ENST00000369020.8	NP_932347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCML4	ENST00000369020.8	c.-60+5760G>A		intron_variant	Intron 1 of 7	5	NM_198081.5	ENSP00000358016.3

Frequencies

GnomAD3 genomes AF: 0.0853 AC: 12971 AN: 152036 Hom.: 586 Cov.: 33

Gnomad AFR AF: 0.0984

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0761

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0394

Gnomad FIN AF: 0.0898

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0750

Gnomad OTH AF: 0.0928

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0853 AC: 12981 AN: 152154 Hom.: 585 Cov.: 33 AF XY: 0.0862 AC XY: 6415 AN XY: 74392

African (AFR) AF: 0.0983 AC: 4079 AN: 41502

American (AMR) AF: 0.0760 AC: 1163 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3466

East Asian (EAS) AF: 0.130 AC: 670 AN: 5172

South Asian (SAS) AF: 0.0396 AC: 191 AN: 4822

European-Finnish (FIN) AF: 0.0898 AC: 950 AN: 10580

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0750 AC: 5097 AN: 68000

Other (OTH) AF: 0.0942 AC: 199 AN: 2112

Alfa AF: 0.0755 Hom.: 973

Bravo AF: 0.0866

Asia WGS AF: 0.0910 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.40
DANN	Benign	0.69
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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: rs17068819; hg19: chr6-108139570;