rs1055607

Variant names:

• chr9-34649053-G-A
• rs1055607
• NM_000155.4:c.876G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-34649053-G-A
• chr9-34649053-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000155.4(GALT):​c.876G>A​(p.Thr292Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00543 in 1,614,048 control chromosomes in the GnomAD database, including 340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (154 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (186 hom.)
• Consequence: GALT NM_000155.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -3.28
• Publications: 7 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

ENSG00000258728 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 9-34649053-G-A is Benign according to our data. Variant chr9-34649053-G-A is described in ClinVar as Benign. ClinVar VariationId is 36158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.28 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000155.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALT	NM_000155.4	MANE Select	c.876G>A	p.Thr292Thr	synonymous	Exon 9 of 11	NP_000146.2
	GALT	NM_001258332.2		c.549G>A	p.Thr183Thr	synonymous	Exon 7 of 9	NP_001245261.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALT	ENST00000378842.8	TSL:1 MANE Select	c.876G>A	p.Thr292Thr	synonymous	Exon 9 of 11	ENSP00000368119.4
	ENSG00000258728	ENST00000556278.1	TSL:5	c.432+597G>A		intron	N/A	ENSP00000451792.1
	GALT	ENST00000450095.6	TSL:2	c.549G>A	p.Thr183Thr	synonymous	Exon 7 of 9	ENSP00000401956.2

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3949 AN: 152084 Hom.: 154 Cov.: 32

Gnomad AFR AF: 0.0878

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.00982

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.0177

GnomAD2 exomes AF: 0.00738 AC: 1855 AN: 251492 AF XY: 0.00572

Gnomad AFR exome AF: 0.0912

Gnomad AMR exome AF: 0.00468

Gnomad ASJ exome AF: 0.00883

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000677

Gnomad OTH exome AF: 0.00537

GnomAD4 exome AF: 0.00329 AC: 4808 AN: 1461846 Hom.: 186 Cov.: 32 AF XY: 0.00290 AC XY: 2110 AN XY: 727226

African (AFR) AF: 0.0933 AC: 3124 AN: 33474

American (AMR) AF: 0.00514 AC: 230 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0100 AC: 262 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.0114 AC: 66 AN: 5768

European-Non Finnish (NFE) AF: 0.000540 AC: 601 AN: 1111982

Other (OTH) AF: 0.00820 AC: 495 AN: 60396

GnomAD4 genome AF: 0.0260 AC: 3955 AN: 152202 Hom.: 154 Cov.: 32 AF XY: 0.0251 AC XY: 1871 AN XY: 74438

African (AFR) AF: 0.0877 AC: 3641 AN: 41500

American (AMR) AF: 0.0126 AC: 192 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00982 AC: 34 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000618 AC: 42 AN: 68010

Other (OTH) AF: 0.0175 AC: 37 AN: 2110

Alfa AF: 0.0106 Hom.: 117

Bravo AF: 0.0302

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.00104

EpiControl AF: 0.000889

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase (5)
-	-	3	not specified (3)
-	-	1	Galactosemia (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.5
DANN	Benign	0.63
PhyloP100		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1055607; hg19: chr9-34649050; COSMIC: COSV58840157; COSMIC: COSV58840157;