chr12-95972733-T-C

Variant names:

• chr12-95972733-T-C
• rs3812807
• NM_002108.4:c.*1499A>G

Variant summary

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

The NM_002108.4(HAL):​c.*1499A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 152,250 control chromosomes in the GnomAD database, including 694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (694 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HAL NM_002108.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.36
• Publications: 2 publications found

Genes affected

HAL (HGNC:4806): (histidine ammonia-lyase) Histidine ammonia-lyase is a cytosolic enzyme catalyzing the first reaction in histidine catabolism, the nonoxidative deamination of L-histidine to trans-urocanic acid. Histidine ammonia-lyase defects cause histidinemia which is characterized by increased histidine and histamine and decreased urocanic acid in body fluids. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

HAL Gene-Disease associations (from GenCC):

• histidinemia

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-95972733-T-C is Benign according to our data. Variant chr12-95972733-T-C is described in ClinVar as Benign. ClinVar VariationId is 310673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002108.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAL	NM_002108.4	MANE Select	c.*1499A>G		3_prime_UTR	Exon 21 of 21	NP_002099.1	P42357-1
	HAL	NM_001258334.2		c.*1627A>G		3_prime_UTR	Exon 20 of 20	NP_001245263.1	P42357-2
	HAL	NM_001258333.2		c.*1499A>G		3_prime_UTR	Exon 20 of 20	NP_001245262.1	P42357-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAL	ENST00000261208.8	TSL:1 MANE Select	c.*1499A>G		3_prime_UTR	Exon 21 of 21	ENSP00000261208.3	P42357-1
	HAL	ENST00000865988.1		c.*1499A>G		3_prime_UTR	Exon 21 of 21	ENSP00000536047.1
	HAL	ENST00000865986.1		c.*1499A>G		3_prime_UTR	Exon 21 of 21	ENSP00000536045.1

Frequencies

GnomAD3 genomes AF: 0.0707 AC: 10759 AN: 152132 Hom.: 691 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.0456

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0467

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0342

Gnomad OTH AF: 0.0718

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0708 AC: 10772 AN: 152250 Hom.: 694 Cov.: 32 AF XY: 0.0730 AC XY: 5432 AN XY: 74456

African (AFR) AF: 0.106 AC: 4396 AN: 41534

American (AMR) AF: 0.0516 AC: 790 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0456 AC: 158 AN: 3468

East Asian (EAS) AF: 0.354 AC: 1827 AN: 5168

South Asian (SAS) AF: 0.123 AC: 596 AN: 4828

European-Finnish (FIN) AF: 0.0467 AC: 496 AN: 10612

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0342 AC: 2327 AN: 68026

Other (OTH) AF: 0.0772 AC: 163 AN: 2112

Alfa AF: 0.0489 Hom.: 575

Bravo AF: 0.0728

Asia WGS AF: 0.237 AC: 825 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Histidinemia (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.95
DANN	Benign	0.53
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs3812807; hg19: chr12-96366511;