chr9-135693771-T-C

Variant names:

• chr9-135693771-T-C
• rs150576747
• NM_001101677.2:c.990A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001101677.2(SOHLH1):​c.990A>G​(p.Pro330Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,581,846 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (9 hom.)
• Consequence: SOHLH1 NM_001101677.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.87
• Publications: 2 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: AD, AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hypogonadism

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 9-135693771-T-C is Benign according to our data. Variant chr9-135693771-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2659711.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.87 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101677.2. 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
	SOHLH1	NM_001101677.2	MANE Select	c.990A>G	p.Pro330Pro	synonymous	Exon 8 of 8	NP_001095147.2	Q5JUK2-2
	SOHLH1	NM_001012415.3		c.*575A>G		3_prime_UTR	Exon 7 of 7	NP_001012415.3	Q5JUK2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOHLH1	ENST00000425225.2	TSL:5 MANE Select	c.990A>G	p.Pro330Pro	synonymous	Exon 8 of 8	ENSP00000404438.1	Q5JUK2-2
	SOHLH1	ENST00000298466.9	TSL:1	c.*575A>G		3_prime_UTR	Exon 7 of 7	ENSP00000298466.5	Q5JUK2-1
	SOHLH1	ENST00000950496.1		c.990A>G	p.Pro330Pro	synonymous	Exon 10 of 10	ENSP00000620555.1

Frequencies

GnomAD3 genomes AF: 0.00130 AC: 198 AN: 152218 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00194

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00168 AC: 331 AN: 197528 AF XY: 0.00183

Gnomad AFR exome AF: 0.0000923

Gnomad AMR exome AF: 0.00231

Gnomad ASJ exome AF: 0.00243

Gnomad EAS exome AF: 0.0000705

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00207

Gnomad OTH exome AF: 0.00333

GnomAD4 exome AF: 0.00151 AC: 2159 AN: 1429510 Hom.: 9 Cov.: 29 AF XY: 0.00161 AC XY: 1143 AN XY: 708066

African (AFR) AF: 0.000337 AC: 11 AN: 32606

American (AMR) AF: 0.00243 AC: 99 AN: 40786

Ashkenazi Jewish (ASJ) AF: 0.00219 AC: 56 AN: 25520

East Asian (EAS) AF: 0.00 AC: 0 AN: 37616

South Asian (SAS) AF: 0.00197 AC: 160 AN: 81260

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50138

Middle Eastern (MID) AF: 0.00905 AC: 52 AN: 5748

European-Non Finnish (NFE) AF: 0.00153 AC: 1673 AN: 1096612

Other (OTH) AF: 0.00182 AC: 108 AN: 59224

GnomAD4 genome AF: 0.00130 AC: 198 AN: 152336 Hom.: 1 Cov.: 33 AF XY: 0.00130 AC XY: 97 AN XY: 74494

African (AFR) AF: 0.000265 AC: 11 AN: 41580

American (AMR) AF: 0.00229 AC: 35 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00194 AC: 132 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00180 Hom.: 1

Bravo AF: 0.00159

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.051
DANN	Benign	0.48
PhyloP100		-5.9
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: rs150576747; hg19: chr9-138585617;