NM_018013.4:c.1382A>C

Variant names:

• chr6-107634226-A-C
• rs587780464
• NM_018013.4:c.1382A>C
• SOBP p.His461Pro

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_018013.4(SOBP):​c.1382A>C​(p.His461Pro) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SOBP NM_018013.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 8.80
• 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: G2P, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP6: Variant 6-107634226-A-C is Benign according to our data. Variant chr6-107634226-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 130357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.1382A>C	p.His461Pro	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.1382A>C	p.His461Pro	missense	Exon 6 of 7	ENSP00000318900.5	A7XYQ1
	SOBP	ENST00000911406.1		c.1382A>C	p.His461Pro	missense	Exon 6 of 7	ENSP00000581465.1
	SOBP	ENST00000911407.1		c.1382A>C	p.His461Pro	missense	Exon 6 of 6	ENSP00000581466.1

Frequencies

GnomAD3 genomes AF: 0.000414 AC: 51 AN: 123192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000536

Gnomad AMI AF: 0.00139

Gnomad AMR AF: 0.000312

Gnomad ASJ AF: 0.000332

Gnomad EAS AF: 0.000230

Gnomad SAS AF: 0.000813

Gnomad FIN AF: 0.000891

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000298

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000414 AC: 59 AN: 1425152 Hom.: 0 Cov.: 32 AF XY: 0.0000395 AC XY: 28 AN XY: 709534

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000304 AC: 1 AN: 32842

American (AMR) AF: 0.0000907 AC: 4 AN: 44100

Ashkenazi Jewish (ASJ) AF: 0.000117 AC: 3 AN: 25668

East Asian (EAS) AF: 0.0000518 AC: 2 AN: 38642

South Asian (SAS) AF: 0.0000833 AC: 7 AN: 84080

European-Finnish (FIN) AF: 0.000128 AC: 5 AN: 39190

Middle Eastern (MID) AF: 0.000181 AC: 1 AN: 5536

European-Non Finnish (NFE) AF: 0.0000310 AC: 34 AN: 1095958

Other (OTH) AF: 0.0000338 AC: 2 AN: 59136

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000414 AC: 51 AN: 123246 Hom.: 0 Cov.: 32 AF XY: 0.000534 AC XY: 32 AN XY: 59928

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000534 AC: 17 AN: 31812

American (AMR) AF: 0.000311 AC: 4 AN: 12852

Ashkenazi Jewish (ASJ) AF: 0.000332 AC: 1 AN: 3014

East Asian (EAS) AF: 0.000231 AC: 1 AN: 4330

South Asian (SAS) AF: 0.000818 AC: 3 AN: 3668

European-Finnish (FIN) AF: 0.000891 AC: 7 AN: 7856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 242

European-Non Finnish (NFE) AF: 0.000298 AC: 17 AN: 57006

Other (OTH) AF: 0.00 AC: 0 AN: 1748

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00581 Hom.: 0

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		8.8
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.32	T
Varity_R		0.35
gMVP		0.47
Mutation Taster		=54/46	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs587780464;

hg19: chr6-107955430;