3-15560857-G-A

Variant names:

• chr3-15560857-G-A
• rs141479215
• NM_012260.4:c.*8C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_012260.4(HACL1):​c.*8C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,593,954 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (7 hom.)
• Consequence: HACL1 NM_012260.4 3_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0110
• Publications: 1 publications found

Genes affected

HACL1 (HGNC:17856): (2-hydroxyacyl-CoA lyase 1) Enables several functions, including 2-hydroxy-3-methylhexadecanoyl-CoA lyase activity; ATP binding activity; and cation binding activity. Involved in fatty acid alpha-oxidation; phytanic acid metabolic process; and protein targeting to peroxisome. Located in nucleoplasm and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-15560857-G-A is Benign according to our data. Variant chr3-15560857-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3038227.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012260.4. 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
	HACL1	NM_012260.4	MANE Select	c.*8C>T		3_prime_UTR	Exon 17 of 17	NP_036392.2	Q9UJ83-1
	HACL1	NM_001284413.2		c.*8C>T		3_prime_UTR	Exon 16 of 16	NP_001271342.1	Q9UJ83-2
	HACL1	NM_001284415.2		c.*8C>T		3_prime_UTR	Exon 15 of 15	NP_001271344.1	Q9UJ83-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HACL1	ENST00000321169.10	TSL:1 MANE Select	c.*8C>T		3_prime_UTR	Exon 17 of 17	ENSP00000323811.5	Q9UJ83-1
	HACL1	ENST00000383779.8	TSL:1	n.*1206C>T		non_coding_transcript_exon	Exon 15 of 15	ENSP00000373289.4	Q7Z773
	HACL1	ENST00000383779.8	TSL:1	n.*1206C>T		3_prime_UTR	Exon 15 of 15	ENSP00000373289.4	Q7Z773

Frequencies

GnomAD3 genomes AF: 0.00186 AC: 283 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00293

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00184 AC: 453 AN: 245940 AF XY: 0.00196

Gnomad AFR exome AF: 0.000869

Gnomad AMR exome AF: 0.000611

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.0000552

Gnomad FIN exome AF: 0.00213

Gnomad NFE exome AF: 0.00284

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.00224 AC: 3233 AN: 1441690 Hom.: 7 Cov.: 26 AF XY: 0.00222 AC XY: 1595 AN XY: 718038

African (AFR) AF: 0.000853 AC: 28 AN: 32842

American (AMR) AF: 0.000652 AC: 28 AN: 42914

Ashkenazi Jewish (ASJ) AF: 0.0000771 AC: 2 AN: 25930

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39558

South Asian (SAS) AF: 0.00164 AC: 139 AN: 84606

European-Finnish (FIN) AF: 0.00262 AC: 140 AN: 53358

Middle Eastern (MID) AF: 0.000700 AC: 4 AN: 5716

European-Non Finnish (NFE) AF: 0.00254 AC: 2784 AN: 1097064

Other (OTH) AF: 0.00179 AC: 107 AN: 59702

GnomAD4 genome AF: 0.00185 AC: 282 AN: 152264 Hom.: 0 Cov.: 32 AF XY: 0.00180 AC XY: 134 AN XY: 74450

African (AFR) AF: 0.000674 AC: 28 AN: 41556

American (AMR) AF: 0.00111 AC: 17 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4824

European-Finnish (FIN) AF: 0.00198 AC: 21 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00291 AC: 198 AN: 68020

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00228 Hom.: 0

Bravo AF: 0.00156

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HACL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.76
PhyloP100		-0.011
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs141479215; hg19: chr3-15602364; COSMIC: COSV100337225; COSMIC: COSV100337225;