chr9-111718282-A-G

Variant names:

• chr9-111718282-A-G
• rs1322257
• NM_001378211.1:c.2138T>C

Variant summary

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

The NM_001378211.1(SHOC1):​c.2138T>C​(p.Ile713Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 1,588,056 control chromosomes in the GnomAD database, including 1,344 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.055 (562 hom., cov: 33)
  • Exomes 𝑓: 0.018 (782 hom.)
• Consequence: SHOC1 NM_001378211.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.840
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• spermatogenic failure

  Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013577342).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHOC1	NM_001378211.1	c.2138T>C	p.Ile713Thr	missense_variant	Exon 16 of 28	ENST00000682961.1	NP_001365140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHOC1	ENST00000682961.1	c.2138T>C	p.Ile713Thr	missense_variant	Exon 16 of 28		NM_001378211.1	ENSP00000508388.1

Frequencies

GnomAD3 genomes AF: 0.0548 AC: 8340 AN: 152162 Hom.: 559 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0236

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.0561

Gnomad FIN AF: 0.00659

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.0444

GnomAD2 exomes AF: 0.0286 AC: 6604 AN: 231244 AF XY: 0.0268

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.0119

Gnomad ASJ exome AF: 0.00399

Gnomad EAS exome AF: 0.0299

Gnomad FIN exome AF: 0.00762

Gnomad NFE exome AF: 0.0120

Gnomad OTH exome AF: 0.0164

GnomAD4 exome AF: 0.0183 AC: 26240 AN: 1435776 Hom.: 782 Cov.: 27 AF XY: 0.0190 AC XY: 13535 AN XY: 713940

African (AFR) AF: 0.168 AC: 5382 AN: 31954

American (AMR) AF: 0.0129 AC: 492 AN: 38004

Ashkenazi Jewish (ASJ) AF: 0.00434 AC: 110 AN: 25326

East Asian (EAS) AF: 0.0225 AC: 879 AN: 39028

South Asian (SAS) AF: 0.0576 AC: 4675 AN: 81180

European-Finnish (FIN) AF: 0.00784 AC: 415 AN: 52966

Middle Eastern (MID) AF: 0.0212 AC: 121 AN: 5702

European-Non Finnish (NFE) AF: 0.0116 AC: 12755 AN: 1102212

Other (OTH) AF: 0.0238 AC: 1411 AN: 59404

GnomAD4 genome AF: 0.0549 AC: 8363 AN: 152280 Hom.: 562 Cov.: 33 AF XY: 0.0541 AC XY: 4027 AN XY: 74462

African (AFR) AF: 0.159 AC: 6622 AN: 41546

American (AMR) AF: 0.0235 AC: 360 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.0245 AC: 127 AN: 5178

South Asian (SAS) AF: 0.0561 AC: 271 AN: 4830

European-Finnish (FIN) AF: 0.00659 AC: 70 AN: 10626

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0115 AC: 784 AN: 68014

Other (OTH) AF: 0.0468 AC: 99 AN: 2116

Alfa AF: 0.0246 Hom.: 641

Bravo AF: 0.0600

TwinsUK AF: 0.0102 AC: 38

ALSPAC AF: 0.0122 AC: 47

ESP6500AA AF: 0.165 AC: 728

ESP6500EA AF: 0.0119 AC: 102

ExAC AF: 0.0323 AC: 3921

Asia WGS AF: 0.0490 AC: 169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.2
DANN	Benign	0.73
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.49	T;T;.
MetaRNN	Benign	0.0014	T;T;T
MetaSVM	Benign	-0.90	T
PhyloP100		0.84
PROVEAN	Benign	1.9	N;N;N
REVEL	Benign	0.014
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.24	T;T;T
Vest4		0.066
MPC		0.14
ClinPred		0.0049	T
GERP RS		2.5
gMVP		0.043
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs1322257; hg19: chr9-114480562; COSMIC: COSV59505631;