Genetic Variant SHOC1:c.46-136C>T (chr9-111786171-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001378211.1(SHOC1):c.46-136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 591,180 control chromosomes in the GnomAD database, including 97,825 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 0.56 ( 24523 hom., cov: 33)

Exomes 𝑓: 0.57 ( 73302 hom. )

Consequence

SHOC1
NM_001378211.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.109

Publications

4 publications found

Variant links:

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

SHOC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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.46-136C>T		intron	N/A	NP_001365140.1
	SHOC1	NR_109816.2		n.120-136C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SHOC1	ENST00000682961.1	MANE Select	c.46-136C>T	intron	N/A	ENSP00000508388.1
SHOC1	ENST00000374283.5	TSL:1	c.46-136C>T	intron	N/A	ENSP00000363401.5
SHOC1	ENST00000683944.1		n.46-136C>T	intron	N/A	ENSP00000507813.1

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

85136

AN:

151904

Hom.:

24491

Cov.:

show subpopulations

Gnomad AFR

AF:

0.480

Gnomad AMI

AF:

0.597

Gnomad AMR

AF:

0.677

Gnomad ASJ

AF:

0.544

Gnomad EAS

AF:

0.870

Gnomad SAS

AF:

0.567

Gnomad FIN

AF:

0.633

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.549

Gnomad OTH

AF:

0.557

GnomAD4 exome

AF:

0.568

AC:

249618

AN:

439158

Hom.:

73302

AF XY:

0.568

AC XY:

126701

AN XY:

222902

show subpopulations

African (AFR)

AF:

0.481

AC:

4848

AN:

10080

American (AMR)

AF:

0.707

AC:

5403

AN:

7642

Ashkenazi Jewish (ASJ)

AF:

0.562

AC:

6047

AN:

10752

East Asian (EAS)

AF:

0.904

AC:

20575

AN:

22756

South Asian (SAS)

AF:

0.542

AC:

9230

AN:

17036

European-Finnish (FIN)

AF:

0.616

AC:

12343

AN:

20044

Middle Eastern (MID)

AF:

0.534

AC:

919

AN:

1722

European-Non Finnish (NFE)

AF:

0.544

AC:

177426

AN:

326334

Other (OTH)

AF:

0.563

AC:

12827

AN:

22792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

5023

10046

15070

20093

25116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3402

6804

10206

13608

17010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.561

AC:

85220

AN:

152022

Hom.:

24523

Cov.:

AF XY:

0.570

AC XY:

42395

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.480

AC:

19887

AN:

41434

American (AMR)

AF:

0.678

AC:

10361

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.544

AC:

1887

AN:

3468

East Asian (EAS)

AF:

0.871

AC:

4520

AN:

5192

South Asian (SAS)

AF:

0.567

AC:

2731

AN:

4820

European-Finnish (FIN)

AF:

0.633

AC:

6682

AN:

10560

Middle Eastern (MID)

AF:

0.561

AC:

165

AN:

294

European-Non Finnish (NFE)

AF:

0.549

AC:

37269

AN:

67942

Other (OTH)

AF:

0.557

AC:

1178

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1890

3780

5671

7561

9451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.564

Hom.:

10188

Bravo

AF:

0.563

Asia WGS

AF:

0.689

AC:

2396

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.5

(source)

DANN

Benign

0.69

PhyloP100

0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over