rs368271940

Variant names:

• chr6-107634654-C-A
• rs368271940
• NM_018013.4:c.1810C>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_018013.4(SOBP):​c.1810C>A​(p.Gln604Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00138 in 1,563,008 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00086 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0014 (3 hom.)
• Consequence: SOBP NM_018013.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• Conservation: PhyloP100: 4.56
• 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: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• syndromic intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014897227).
• BP6: Variant 6-107634654-C-A is Benign according to our data. Variant chr6-107634654-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 130358.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018013.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOBP	NM_018013.4	MANE Select	c.1810C>A	p.Gln604Lys	missense	Exon 6 of 7	NP_060483.3	A7XYQ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOBP	ENST00000317357.10	TSL:5 MANE Select	c.1810C>A	p.Gln604Lys	missense	Exon 6 of 7	ENSP00000318900.5	A7XYQ1
	SOBP	ENST00000911406.1		c.1810C>A	p.Gln604Lys	missense	Exon 6 of 7	ENSP00000581465.1
	SOBP	ENST00000911407.1		c.1810C>A	p.Gln604Lys	missense	Exon 6 of 6	ENSP00000581466.1

Frequencies

GnomAD3 genomes AF: 0.000857 AC: 130 AN: 151656 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000285

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00167

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000721 AC: 118 AN: 163742 AF XY: 0.000679

Gnomad AFR exome AF: 0.000358

Gnomad AMR exome AF: 0.0000697

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000264

Gnomad NFE exome AF: 0.00161

Gnomad OTH exome AF: 0.000656

GnomAD4 exome AF: 0.00143 AC: 2025 AN: 1411242 Hom.: 3 Cov.: 33 AF XY: 0.00136 AC XY: 950 AN XY: 699346

African (AFR) AF: 0.000247 AC: 8 AN: 32432

American (AMR) AF: 0.000173 AC: 7 AN: 40478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25452

East Asian (EAS) AF: 0.00 AC: 0 AN: 37450

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82560

European-Finnish (FIN) AF: 0.000279 AC: 10 AN: 35888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5516

European-Non Finnish (NFE) AF: 0.00174 AC: 1905 AN: 1092798

Other (OTH) AF: 0.00160 AC: 94 AN: 58668

GnomAD4 genome AF: 0.000857 AC: 130 AN: 151766 Hom.: 0 Cov.: 31 AF XY: 0.000688 AC XY: 51 AN XY: 74180

African (AFR) AF: 0.000241 AC: 10 AN: 41478

American (AMR) AF: 0.000197 AC: 3 AN: 15264

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5062

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000285 AC: 3 AN: 10524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00167 AC: 113 AN: 67830

Other (OTH) AF: 0.000475 AC: 1 AN: 2104

Alfa AF: 0.000790 Hom.: 0

Bravo AF: 0.000873

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000755 AC: 5

ExAC AF: 0.000707 AC: 78

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	not provided (2)
-	1	-	Intellectual disability, anterior maxillary protrusion, and strabismus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.033
Eigen_PC	Benign	-0.032
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		4.6
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.087
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.91	T
Polyphen		0.95	P
Vest4		0.41
MVP		0.040
ClinPred		0.062	T
GERP RS		3.9
Varity_R		0.27
gMVP		0.44
Mutation Taster		=84/16	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: rs368271940; hg19: chr6-107955858;