rs200685194

Variant names:

• chr6-107634573-C-A
• rs200685194
• NM_018013.4:c.1729C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-107634573-C-A
• chr6-107634573-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018013.4(SOBP):​c.1729C>A​(p.Pro577Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. P577S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SOBP NM_018013.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.607
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05748862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOBP	NM_018013.4	c.1729C>A	p.Pro577Thr	missense_variant	Exon 6 of 7	ENST00000317357.10	NP_060483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOBP	ENST00000317357.10	c.1729C>A	p.Pro577Thr	missense_variant	Exon 6 of 7	5	NM_018013.4	ENSP00000318900.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453370 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 723350

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111748

Other (OTH) AF: 0.00 AC: 0 AN: 60280

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.61
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.028
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.32	T
Vest4		0.073
ClinPred		0.078	T
GERP RS		0.48
Varity_R		0.10
gMVP		0.44
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: rs200685194; hg19: chr6-107955777;