rs953536

Variant names:

• chr9-111727607-C-T
• rs953536
• NM_001378211.1:c.1834+26G>A

Variant summary

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

The NM_001378211.1(SHOC1):​c.1834+26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,527,950 control chromosomes in the GnomAD database, including 240,076 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.55 (23649 hom., cov: 32)
  • Exomes 𝑓: 0.56 (216427 hom.)
• Consequence: SHOC1 NM_001378211.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.703
• 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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378211.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHOC1	NM_001378211.1	MANE Select	c.1834+26G>A		intron	N/A	NP_001365140.1	A0A804HLJ8
	SHOC1	NM_173521.5		c.1642+26G>A		intron	N/A	NP_775792.5	Q5VXU9-1
	SHOC1	NM_001080551.3		c.1525+26G>A		intron	N/A	NP_001074020.3	Q5VXU9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHOC1	ENST00000682961.1	MANE Select	c.1834+26G>A		intron	N/A	ENSP00000508388.1	A0A804HLJ8
	SHOC1	ENST00000318737.8	TSL:1	c.1642+26G>A		intron	N/A	ENSP00000322108.4	Q5VXU9-1
	SHOC1	ENST00000394777.8	TSL:1	c.1525+26G>A		intron	N/A	ENSP00000378257.4	A6PVK7

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83500 AN: 151846 Hom.: 23628 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.550

GnomAD2 exomes AF: 0.597 AC: 113130 AN: 189404 AF XY: 0.591

Gnomad AFR exome AF: 0.458

Gnomad AMR exome AF: 0.723

Gnomad ASJ exome AF: 0.550

Gnomad EAS exome AF: 0.872

Gnomad FIN exome AF: 0.623

Gnomad NFE exome AF: 0.548

Gnomad OTH exome AF: 0.578

GnomAD4 exome AF: 0.556 AC: 765111 AN: 1375986 Hom.: 216427 Cov.: 27 AF XY: 0.556 AC XY: 376503 AN XY: 677374

African (AFR) AF: 0.461 AC: 14090 AN: 30562

American (AMR) AF: 0.705 AC: 22026 AN: 31242

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 11977 AN: 21344

East Asian (EAS) AF: 0.892 AC: 34578 AN: 38776

South Asian (SAS) AF: 0.552 AC: 37886 AN: 68650

European-Finnish (FIN) AF: 0.620 AC: 31025 AN: 50076

Middle Eastern (MID) AF: 0.554 AC: 2964 AN: 5350

European-Non Finnish (NFE) AF: 0.540 AC: 579070 AN: 1073102

Other (OTH) AF: 0.554 AC: 31495 AN: 56884

GnomAD4 genome AF: 0.550 AC: 83573 AN: 151964 Hom.: 23649 Cov.: 32 AF XY: 0.560 AC XY: 41575 AN XY: 74278

African (AFR) AF: 0.460 AC: 19049 AN: 41434

American (AMR) AF: 0.642 AC: 9798 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1897 AN: 3466

East Asian (EAS) AF: 0.870 AC: 4503 AN: 5176

South Asian (SAS) AF: 0.562 AC: 2714 AN: 4826

European-Finnish (FIN) AF: 0.632 AC: 6680 AN: 10566

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37060 AN: 67920

Other (OTH) AF: 0.550 AC: 1160 AN: 2110

Alfa AF: 0.546 Hom.: 63754

Bravo AF: 0.549

Asia WGS AF: 0.679 AC: 2360 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.54
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs953536; hg19: chr9-114489887;