2-61083158-A-G

Position:

• chr2-61083158-A-G

Variant summary

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

The NM_001129993.3(SANBR):​c.734A>G​(p.Glu245Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,454,406 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: SANBR NM_001129993.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.04

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.734A>G	p.Glu245Gly	missense_variant	8/22	ENST00000402291.6	NP_001123465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SANBR	ENST00000402291.6	c.734A>G	p.Glu245Gly	missense_variant	8/22	1	NM_001129993.3	ENSP00000385579.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000807 AC: 2 AN: 247980 Hom.: 0 AF XY: 0.00000747 AC XY: 1 AN XY: 133812

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000124 AC: 18 AN: 1454406 Hom.: 0 Cov.: 28 AF XY: 0.0000138 AC XY: 10 AN XY: 723518

Gnomad4 AFR exome AF: 0.0000301

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: 0.0000153

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

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

Sep 25, 2023

The c.734A>G (p.E245G) alteration is located in exon 8 (coding exon 6) of the KIAA1841 gene. This alteration results from a A to G substitution at nucleotide position 734, causing the glutamic acid (E) at amino acid position 245 to be replaced by a glycine (G). 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	Benign	0.18
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.35	T;.;T;.;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.087
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	.;.;T;T;T
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.66	D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;M;M;.;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-4.3	D;D;D;.;D
REVEL	Benign	0.26
Sift	Uncertain	0.017	D;D;D;.;D
Sift4G	Uncertain	0.010	D;D;D;D;D
Polyphen		0.050	B;B;B;.;B
Vest4		0.73
MutPred		0.25		Gain of catalytic residue at C247 (P = 0.0738);Gain of catalytic residue at C247 (P = 0.0738);Gain of catalytic residue at C247 (P = 0.0738);.;Gain of catalytic residue at C247 (P = 0.0738);
MVP		0.57
MPC		0.21
ClinPred		0.77	D
GERP RS		4.0
Varity_R		0.29
gMVP		0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs775107015; hg19: chr2-61310293;