9-34646343-G-T

Variant names:

• chr9-34646343-G-T
• rs12551313
• ENST00000605275.1:n.209-334G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000605275.1(GALT):​n.209-334G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 152,312 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.028 (101 hom., cov: 32)
• Consequence: GALT ENST00000605275.1 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.171
• Publications: 0 publications found

Genes affected

GALT (HGNC:4135): (galactose-1-phosphate uridylyltransferase) Galactose-1-phosphate uridyl transferase (GALT) catalyzes the second step of the Leloir pathway of galactose metabolism, namely the conversion of UDP-glucose + galactose-1-phosphate to glucose-1-phosphate + UDP-galactose. The absence of this enzyme results in classic galactosemia in humans and can be fatal in the newborn period if lactose is not removed from the diet. The pathophysiology of galactosemia has not been clearly defined. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

GALT Gene-Disease associations (from GenCC):

• classic galactosemia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• galactosemia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Myriad Women’s Health

ENSG00000294190 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-34646343-G-T is Benign according to our data. Variant chr9-34646343-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1196736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALT	ENST00000605275.1	n.209-334G>T		intron_variant	Intron 1 of 1	3
ENSG00000294190	ENST00000721802.1	n.127-1729C>A		intron_variant	Intron 1 of 2
GALT	ENST00000450095.6	c.-564G>T		upstream_gene_variant		2		ENSP00000401956.2

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 4253 AN: 152194 Hom.: 102 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0427

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0354

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0279 AC: 4251 AN: 152312 Hom.: 101 Cov.: 32 AF XY: 0.0292 AC XY: 2178 AN XY: 74486

African (AFR) AF: 0.0120 AC: 497 AN: 41574

American (AMR) AF: 0.0222 AC: 340 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0600 AC: 208 AN: 3468

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5180

South Asian (SAS) AF: 0.103 AC: 497 AN: 4824

European-Finnish (FIN) AF: 0.0427 AC: 453 AN: 10616

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0309 AC: 2103 AN: 68028

Other (OTH) AF: 0.0350 AC: 74 AN: 2112

Alfa AF: 0.0275 Hom.: 8

Bravo AF: 0.0234

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 11, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.58
PhyloP100		0.17
PromoterAI		-0.0092	Neutral

Splicing

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

Other links and lift over

dbSNP: rs12551313; hg19: chr9-34646340;