chr9-135693799-C-T

Variant names:

• chr9-135693799-C-T
• rs1263504676
• NM_001101677.2:c.962G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001101677.2(SOHLH1):​c.962G>A​(p.Arg321Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000914 in 1,422,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000091 (0 hom.)
• Consequence: SOHLH1 NM_001101677.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.271
• Publications: 1 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):

• spermatogenic failure 32

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• ovarian dysgenesis 5

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

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22314441).

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.962G>A	p.Arg321Gln	missense	Exon 8 of 8	NP_001095147.2	Q5JUK2-2
	SOHLH1	NM_001012415.3		c.*547G>A		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.962G>A	p.Arg321Gln	missense	Exon 8 of 8	ENSP00000404438.1	Q5JUK2-2
	SOHLH1	ENST00000298466.9	TSL:1	c.*547G>A		3_prime_UTR	Exon 7 of 7	ENSP00000298466.5	Q5JUK2-1
	SOHLH1	ENST00000950496.1		c.962G>A	p.Arg321Gln	missense	Exon 10 of 10	ENSP00000620555.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000106 AC: 2 AN: 189122 AF XY: 0.00

Gnomad AFR exome AF: 0.0000978

Gnomad AMR exome AF: 0.0000348

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000914 AC: 13 AN: 1422204 Hom.: 0 Cov.: 29 AF XY: 0.00000569 AC XY: 4 AN XY: 703314

African (AFR) AF: 0.0000308 AC: 1 AN: 32432

American (AMR) AF: 0.0000250 AC: 1 AN: 39958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25458

East Asian (EAS) AF: 0.00 AC: 0 AN: 37230

South Asian (SAS) AF: 0.00 AC: 0 AN: 80894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.0000101 AC: 11 AN: 1091832

Other (OTH) AF: 0.00 AC: 0 AN: 58908

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Benign	0.93
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.27
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.078
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.20	T
Polyphen		0.89	P
Vest4		0.39
MVP		0.43
MPC		0.041
ClinPred		0.11	T
GERP RS		1.4
gMVP		0.057
Mutation Taster		=94/6	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: rs1263504676; hg19: chr9-138585645;