2-44944703-A-C

Variant names:

• chr2-44944703-A-C
• rs338074
• NM_005413.4:c.942A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005413.4(SIX3):​c.942A>C​(p.Ala314Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A314A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SIX3 NM_005413.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128
• Publications: 20 publications found

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]

SIX3-AS1 (HGNC:40532): (SIX3 antisense RNA 1)

ENSG00000225156 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=0.128 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIX3	NM_005413.4	c.942A>C	p.Ala314Ala	synonymous_variant	Exon 2 of 2	ENST00000260653.5	NP_005404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIX3	ENST00000260653.5	c.942A>C	p.Ala314Ala	synonymous_variant	Exon 2 of 2	1	NM_005413.4	ENSP00000260653.3
SIX3-AS1	ENST00000760561.1	n.49T>G		non_coding_transcript_exon_variant	Exon 1 of 2
ENSG00000225156	ENST00000760330.1	n.135+10327A>C		intron_variant	Intron 1 of 1
SIX3-AS1	ENST00000760560.1	n.388+695T>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 68

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		0.13
Mutation Taster		=99/1	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: rs338074; hg19: chr2-45171842;