chr2-61077050-G-A

Position:

• chr2-61077050-G-A

Variant summary

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

The NM_001129993.3(SANBR):​c.562G>A​(p.Glu188Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: SANBR NM_001129993.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.96

Genes affected

SANBR (HGNC:29387): (SANT and BTB domain regulator of CSR)

SANBR (HGNC:):

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	Protein	UniProt
SANBR	NM_001129993.3	c.562G>A	p.Glu188Lys	missense_variant	6/22	ENST00000402291.6	NP_001123465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SANBR	ENST00000402291.6	c.562G>A	p.Glu188Lys	missense_variant	6/22	1	NM_001129993.3	ENSP00000385579.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461684 Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6 AN XY: 727148

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2022

The c.562G>A (p.E188K) alteration is located in exon 6 (coding exon 4) of the KIAA1841 gene. This alteration results from a G to A substitution at nucleotide position 562, causing the glutamic acid (E) at amino acid position 188 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.34	T;.;T;.;.
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	.;.;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.57	D;D;D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.8	M;M;M;.;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.2	D;D;D;.;D
REVEL	Benign	0.27
Sift	Uncertain	0.0030	D;D;D;.;D
Sift4G	Uncertain	0.012	D;D;D;D;D
Polyphen		1.0	D;D;D;.;D
Vest4		0.66
MutPred		0.38		Gain of ubiquitination at E188 (P = 0.0146);Gain of ubiquitination at E188 (P = 0.0146);Gain of ubiquitination at E188 (P = 0.0146);.;Gain of ubiquitination at E188 (P = 0.0146);
MVP		0.53
MPC		0.26
ClinPred		0.97	D
GERP RS		4.9
Varity_R		0.65
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-61304185;