rs1160844516

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001101677.2(SOHLH1):​c.985G>C​(p.Ala329Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,429,392 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A329T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 7.0e-7 ( 0 hom. )

Consequence

SOHLH1
NM_001101677.2 missense

Scores

3
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0970
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1359593).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SOHLH1NM_001101677.2 linkc.985G>C p.Ala329Pro missense_variant Exon 8 of 8 ENST00000425225.2 NP_001095147.2 Q5JUK2-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SOHLH1ENST00000425225.2 linkc.985G>C p.Ala329Pro missense_variant Exon 8 of 8 5 NM_001101677.2 ENSP00000404438.1 Q5JUK2-2
SOHLH1ENST00000298466 linkc.*570G>C 3_prime_UTR_variant Exon 7 of 7 1 ENSP00000298466.5 Q5JUK2-1
SOHLH1ENST00000673731.1 linkc.409G>C p.Ala137Pro missense_variant Exon 5 of 5 ENSP00000501311.1 A0A669KBI8
SOHLH1ENST00000674066.1 linkn.2575G>C non_coding_transcript_exon_variant Exon 11 of 11

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000506
AC:
1
AN:
197698
Hom.:
0
AF XY:
0.00000934
AC XY:
1
AN XY:
107118
show subpopulations
Gnomad AFR exome
AF:
0.0000921
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
7.00e-7
AC:
1
AN:
1429392
Hom.:
0
Cov.:
29
AF XY:
0.00000141
AC XY:
1
AN XY:
707982
show subpopulations
Gnomad4 AFR exome
AF:
0.0000307
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:
0.00
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
Uncertain
0.99
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.55
FATHMM_MKL
Benign
0.018
N
LIST_S2
Benign
0.38
T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.062
Sift
Uncertain
0.028
D
Sift4G
Benign
0.10
T
Polyphen
1.0
D
Vest4
0.20
MutPred
0.079
Gain of glycosylation at A329 (P = 0.0169);
MVP
0.29
MPC
0.28
ClinPred
0.19
T
GERP RS
1.4
gMVP
0.050

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1160844516; hg19: chr9-138585622; API