chr6-107490654-A-G

Variant names:

• chr6-107490654-A-G
• rs746140922
• NM_018013.4:c.38A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_018013.4(SOBP):​c.38A>G​(p.Asn13Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,608,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: SOBP NM_018013.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.33
• Publications: 0 publications found

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]

SOBP Gene-Disease associations (from GenCC):

• intellectual disability, anterior maxillary protrusion, and strabismus

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• syndromic intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011476219).
• BP6: Variant 6-107490654-A-G is Benign according to our data. Variant chr6-107490654-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 798033.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOBP	NM_018013.4	c.38A>G	p.Asn13Ser	missense_variant	Exon 1 of 7	ENST00000317357.10	NP_060483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOBP	ENST00000317357.10	c.38A>G	p.Asn13Ser	missense_variant	Exon 1 of 7	5	NM_018013.4	ENSP00000318900.5
SOBP	ENST00000618129.1	c.38A>G	p.Asn13Ser	missense_variant	Exon 1 of 4	1		ENSP00000478366.1
SOBP	ENST00000477448.1	n.549A>G		non_coding_transcript_exon_variant	Exon 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152038 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000121 AC: 29 AN: 238736 AF XY: 0.000123

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00153

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000170

GnomAD4 exome AF: 0.0000172 AC: 25 AN: 1456930 Hom.: 0 Cov.: 30 AF XY: 0.0000166 AC XY: 12 AN XY: 724064

African (AFR) AF: 0.00 AC: 0 AN: 33390

American (AMR) AF: 0.00 AC: 0 AN: 44150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26060

East Asian (EAS) AF: 0.000606 AC: 24 AN: 39590

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109404

Other (OTH) AF: 0.00 AC: 0 AN: 60204

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152038 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74264

African (AFR) AF: 0.00 AC: 0 AN: 41406

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.000141 AC: 17

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T;.
Eigen	Benign	0.013
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.011	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.69	N;.
PhyloP100		5.3
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.15
Sift	Benign	0.18	T;.
Sift4G	Benign	0.27	T;T
Polyphen		0.75	P;.
Vest4		0.26
MutPred		0.11		Gain of phosphorylation at N13 (P = 0.0047);Gain of phosphorylation at N13 (P = 0.0047);
MVP		0.048
ClinPred		0.061	T
GERP RS		4.9
PromoterAI		-0.0095	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.66
Mutation Taster		=93/7	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: rs746140922; hg19: chr6-107811858;