rs146747167

chr6-107634459-A-Cchr6-107634459-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018013.4(SOBP):c.1615A>C(p.Ile539Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,458,390 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I539V) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SOBP NM_018013.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.63

Genes affected

SOBP (HGNC:29256): (sine oculis binding protein homolog) The protein encoded by this gene is a nuclear zinc finger protein that is involved in development of the cochlea. Defects in this gene have also been linked to intellectual disability. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOBP	NM_018013.4	c.1615A>C	p.Ile539Leu	missense_variant	6/7	ENST00000317357.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOBP	ENST00000317357.10	c.1615A>C	p.Ile539Leu	missense_variant	6/7	5	NM_018013.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458390 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 725644

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000199

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
Cadd	Pathogenic	26
Dann	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.16
Sift	Benign	0.21	T
Sift4G	Benign	0.095	T
Polyphen		0.98	D
Vest4		0.66
MutPred		0.27		Gain of catalytic residue at I539 (P = 0.001);
MVP		0.092
ClinPred		0.93	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.33
gMVP		0.58

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

Other links and lift over

dbSNP: rs146747167; hg19: chr6-107955663;