6-107720864-C-G

Position:

• chr6-107720864-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198081.5(SCML4):​c.812G>C​(p.Arg271Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SCML4 NM_198081.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.295

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]

SCML4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11535877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCML4	NM_198081.5	c.812G>C	p.Arg271Thr	missense_variant	6/8	ENST00000369020.8	NP_932347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCML4	ENST00000369020.8	c.812G>C	p.Arg271Thr	missense_variant	6/8	5	NM_198081.5	ENSP00000358016.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251376 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135860

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2024

The c.812G>C (p.R271T) alteration is located in exon 6 (coding exon 5) of the SCML4 gene. This alteration results from a G to C substitution at nucleotide position 812, causing the arginine (R) at amino acid position 271 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.0061	.;.;T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;.;L;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.073
Sift	Benign	0.38	T;D;T;D
Sift4G	Benign	0.56	T;D;T;D
Polyphen		0.41, 0.87	.;.;B;P
Vest4		0.47
MutPred		0.22		.;.;Gain of glycosylation at R271 (P = 0.0609);.;
MVP		0.50
MPC		0.23
ClinPred		0.58	D
GERP RS		2.5
Varity_R		0.074
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs758974871; hg19: chr6-108042068;