rs1344650194

chr2-44942273-G-Achr2-44942273-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005413.4(SIX3):c.169G>A(p.Gly57Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 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. G57C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SIX3 NM_005413.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

Genes affected

SIX3 (HGNC:10889): (SIX homeobox 3) This gene encodes a member of the sine oculis homeobox transcription factor family. The encoded protein plays a role in eye development. Mutations in this gene have been associated with holoprosencephaly type 2. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23149729).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIX3	NM_005413.4	c.169G>A	p.Gly57Ser	missense_variant	1/2	ENST00000260653.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIX3	ENST00000260653.5	c.169G>A	p.Gly57Ser	missense_variant	1/2	1	NM_005413.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1384510 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 683900

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
Cadd	Benign	21
Dann	Uncertain	0.98
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.62	T
M_CAP	Pathogenic	0.77	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.34	N
REVEL	Benign	0.17
Sift	Benign	0.22	T
Sift4G	Benign	0.061	T
Polyphen		0.038	B
Vest4		0.30
MutPred		0.26		Gain of glycosylation at G57 (P = 7e-04);
MVP		0.98
MPC		1.0
ClinPred		0.092	T
GERP RS		2.7
Varity_R		0.086
gMVP		0.59

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: rs1344650194; hg19: chr2-45169412;