4-75940132-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_014435.4(NAAA):c.240C>T(p.Ile80=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,614,080 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (6 hom.)
• Consequence: NAAA NM_014435.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.736

Genes affected

NAAA (HGNC:736): (N-acylethanolamine acid amidase) Enables N-(long-chain-acyl)ethanolamine deacylase activity; N-acylsphingosine amidohydrolase activity; and fatty acid amide hydrolase activity. Involved in several processes, including N-acylethanolamine metabolic process; N-acylphosphatidylethanolamine metabolic process; and sphingosine metabolic process. Located in lysosome. Is extrinsic component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 4-75940132-G-A is Benign according to our data. Variant chr4-75940132-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 717150.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.736 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAAA	NM_014435.4	c.240C>T	p.Ile80=	synonymous_variant	2/11	ENST00000286733.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAAA	ENST00000286733.9	c.240C>T	p.Ile80=	synonymous_variant	2/11	5	NM_014435.4	P1

Frequencies

GnomAD3 genomes AF: 0.00103 AC: 157 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00157

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00123 AC: 306 AN: 249318 Hom.: 0 AF XY: 0.00129 AC XY: 175 AN XY: 135350

Gnomad AFR exome AF: 0.000388

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00517

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000523

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.00147

Gnomad OTH exome AF: 0.00297

GnomAD4 exome AF: 0.00111 AC: 1625 AN: 1461776 Hom.: 6 Cov.: 34 AF XY: 0.00118 AC XY: 860 AN XY: 727192

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.00605

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000974

Gnomad4 FIN exome AF: 0.0000938

Gnomad4 NFE exome AF: 0.00100

Gnomad4 OTH exome AF: 0.00195

GnomAD4 genome AF: 0.00103 AC: 157 AN: 152304 Hom.: 0 Cov.: 33 AF XY: 0.000980 AC XY: 73 AN XY: 74462

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00157

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00133 Hom.: 0

Bravo AF: 0.000975

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00273

EpiControl AF: 0.00231

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.5
Dann	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs192282293; hg19: chr4-76861285;