9-135694450-A-G

Variant names:

• chr9-135694450-A-G
• rs374426154
• NM_001101677.2:c.883T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_001101677.2(SOHLH1):​c.883T>C​(p.Leu295Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,612,972 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 Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: SOHLH1 NM_001101677.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.20
• Publications: 0 publications found

Genes affected

SOHLH1 (HGNC:27845): (spermatogenesis and oogenesis specific basic helix-loop-helix 1) This gene encodes one of testis-specific transcription factors which are essential for spermatogenesis, oogenesis and folliculogenesis. This gene is located on chromosome 9. Mutations in this gene are associated with nonobstructive azoospermia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2013]

SOHLH1 Gene-Disease associations (from GenCC):

• ovarian dysgenesis 5

  Inheritance: AR, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hypogonadism

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 9-135694450-A-G is Benign according to our data. Variant chr9-135694450-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3048875.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.2 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOHLH1	NM_001101677.2	c.883T>C	p.Leu295Leu	synonymous_variant	Exon 7 of 8	ENST00000425225.2	NP_001095147.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOHLH1	ENST00000425225.2	c.883T>C	p.Leu295Leu	synonymous_variant	Exon 7 of 8	5	NM_001101677.2	ENSP00000404438.1
SOHLH1	ENST00000298466.9	c.883T>C	p.Leu295Leu	synonymous_variant	Exon 7 of 7	1		ENSP00000298466.5
SOHLH1	ENST00000673731.1	c.241T>C	p.Leu81Leu	synonymous_variant	Exon 3 of 5			ENSP00000501311.1
SOHLH1	ENST00000674066.1	n.2473T>C		non_coding_transcript_exon_variant	Exon 10 of 11

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152158 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000206 AC: 51 AN: 248092 AF XY: 0.000163

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000811

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000198

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000195 AC: 285 AN: 1460814 Hom.: 0 Cov.: 79 AF XY: 0.000178 AC XY: 129 AN XY: 726708

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.000716 AC: 32 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000221 AC: 246 AN: 1111962

Other (OTH) AF: 0.0000828 AC: 5 AN: 60380

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152158 Hom.: 0 Cov.: 34 AF XY: 0.0000404 AC XY: 3 AN XY: 74326

African (AFR) AF: 0.0000241 AC: 1 AN: 41428

American (AMR) AF: 0.000131 AC: 2 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000194 Hom.: 0

Bravo AF: 0.000113

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SOHLH1-related disorder Benign:1

Nov 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.18
DANN	Benign	0.36
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

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: rs374426154; hg19: chr9-138586296;