9-135693799-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001101677.2(SOHLH1):​c.962G>T​(p.Arg321Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000281 in 1,422,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: SOHLH1 NM_001101677.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.271

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3274719).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOHLH1	NM_001101677.2	c.962G>T	p.Arg321Leu	missense_variant	Exon 8 of 8	ENST00000425225.2	NP_001095147.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOHLH1	ENST00000425225.2	c.962G>T	p.Arg321Leu	missense_variant	Exon 8 of 8	5	NM_001101677.2	ENSP00000404438.1
SOHLH1	ENST00000298466	c.*547G>T		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000298466.5
SOHLH1	ENST00000673731.1	c.386G>T	p.Arg129Leu	missense_variant	Exon 5 of 5			ENSP00000501311.1
SOHLH1	ENST00000674066.1	n.2552G>T		non_coding_transcript_exon_variant	Exon 11 of 11

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000281 AC: 4 AN: 1422206 Hom.: 0 Cov.: 29 AF XY: 0.00000284 AC XY: 2 AN XY: 703316

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000366

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.97
Eigen	Benign	0.00015
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.96	T
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.098
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.36
MutPred		0.28		Loss of methylation at R321 (P = 0.0055);
MVP		0.50
MPC		0.041
ClinPred		0.41	T
GERP RS		1.4
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-138585645; COSMIC: COSV53682528;