chr9-111700047-C-A

Position:

• chr9-111700047-C-A

Variant summary

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

The NM_001378211.1(SHOC1):​c.3090G>T​(p.Glu1030Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000757 in 1,320,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: SHOC1 NM_001378211.1 missense, splice_region
• Scores: Splicing: ADA: 0.9811
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.630

Genes affected

SHOC1 (HGNC:26535): (shortage in chiasmata 1) Enables single-stranded DNA binding activity. Predicted to be involved in resolution of meiotic recombination intermediates. Predicted to be located in chromosome. Predicted to be active in condensed nuclear chromosome. [provided by Alliance of Genome Resources, Apr 2022]

SHOC1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHOC1	NM_001378211.1	c.3090G>T	p.Glu1030Asp	missense_variant, splice_region_variant	24/28	ENST00000682961.1	NP_001365140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHOC1	ENST00000682961.1	c.3090G>T	p.Glu1030Asp	missense_variant, splice_region_variant	24/28		NM_001378211.1	ENSP00000508388.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.57e-7 AC: 1 AN: 1320576 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 662774

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: 0.00000101

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

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.2898G>T (p.E966D) alteration is located in exon 22 (coding exon 21) of the C9orf84 gene. This alteration results from a G to T substitution at nucleotide position 2898, causing the glutamic acid (E) at amino acid position 966 to be replaced by an aspartic acid (D). 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	0.15
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Benign	0.013
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.71	T;T;T;.
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-1.5	N;N;N;N
REVEL	Benign	0.049
Sift	Benign	0.20	T;T;T;T
Sift4G	Uncertain	0.045	D;D;D;D
Vest4		0.090
MutPred		0.20		.;.;Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);
MVP		0.067
MPC		0.098
ClinPred		0.49	T
GERP RS		5.2
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.98
dbscSNV1_RF	Benign	0.68
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.36		Position offset: 0

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-114462327;