chr9-111686859-A-G

Position:

• chr9-111686859-A-G

Variant summary

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

The NM_001378211.1(SHOC1):​c.4438T>C​(p.Ser1480Pro) 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. 12/18 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)
• Consequence: SHOC1 NM_001378211.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22

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]

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=0.08867502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHOC1	NM_001378211.1	c.4438T>C	p.Ser1480Pro	missense_variant	28/28	ENST00000682961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHOC1	ENST00000682961.1	c.4438T>C	p.Ser1480Pro	missense_variant	28/28		NM_001378211.1	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Aug 10, 2021

The c.4246T>C (p.S1416P) alteration is located in exon 26 (coding exon 25) of the C9orf84 gene. This alteration results from a T to C substitution at nucleotide position 4246, causing the serine (S) at amino acid position 1416 to be replaced by a proline (P). 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	0.087
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	1.0
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.67	T;T;T;.
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.089	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.85	N;N;N;N
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.032
Sift	Uncertain	0.013	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Vest4		0.24
MutPred		0.24		.;.;Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);
MVP		0.055
MPC		0.17
ClinPred		0.54	D
GERP RS		2.6
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-114449139;