8-144333755-G-C

Position:

• chr8-144333755-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_031309.6(SCRT1):​c.477C>G​(p.Ser159Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,011,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: SCRT1 NM_031309.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.196

Genes affected

SCRT1 (HGNC:15950): (scratch family transcriptional repressor 1) This gene encodes a C2H2-type zinc finger transcriptional repressor that binds to E-box motifs. The encoded protein may promote neural differention and may be involved in cancers with neuroendocrine features. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07407349).
• BS2: High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCRT1	NM_031309.6	c.477C>G	p.Ser159Arg	missense_variant	2/2	ENST00000569446.3	NP_112599.2
SCRT1	XM_024447291.2	c.276C>G	p.Ser92Arg	missense_variant	2/2		XP_024303059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCRT1	ENST00000569446.3	c.477C>G	p.Ser159Arg	missense_variant	2/2	1	NM_031309.6	ENSP00000455711.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000218 AC: 22 AN: 1011436 Hom.: 0 Cov.: 30 AF XY: 0.0000210 AC XY: 10 AN XY: 476088

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000251

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Oct 08, 2024

The c.477C>G (p.S159R) alteration is located in exon 2 (coding exon 2) of the SCRT1 gene. This alteration results from a C to G substitution at nucleotide position 477, causing the serine (S) at amino acid position 159 to be replaced by an arginine (R). 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	Uncertain	0.49
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.5
DANN	Benign	0.21
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.13	N
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.95	T
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.29	N
Sift	Benign	0.25	T
Sift4G	Benign	0.52	T
Vest4		0.16
MutPred		0.46		Loss of phosphorylation at S159 (P = 0.0041);
MVP		0.048
ClinPred		0.067	T
GERP RS		0.72
gMVP		0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs1817838766; hg19: chr8-145557417;