rs17158455

Positions:

• chr11-63631205-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_015459.5(ATL3):​c.1374A>G​(p.Ser458=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,614,212 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0087 (18 hom., cov: 32)
  • Exomes 𝑓: 0.00084 (13 hom.)
• Consequence: ATL3 NM_015459.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -6.38

Genes affected

ATL3 (HGNC:24526): (atlastin GTPase 3) This gene encodes a member of a family of dynamin-like, integral membrane GTPases. The encoded protein is required for the proper formation of the network of interconnected tubules of the endoplasmic reticulum. Mutations in this gene may be associated with hereditary sensory neuropathy type IF. Alternatively spliced transcript variants that encode distinct isoforms have been described. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-63631205-T-C is Benign according to our data. Variant chr11-63631205-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 474832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-63631205-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-6.38 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00871 (1327/152318) while in subpopulation AFR AF= 0.0302 (1256/41580). AF 95% confidence interval is 0.0288. There are 18 homozygotes in gnomad4. There are 651 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1327 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATL3	NM_015459.5	c.1374A>G	p.Ser458=	synonymous_variant	12/13	ENST00000398868.8	NP_056274.3
ATL3	NM_001290048.2	c.1320A>G	p.Ser440=	synonymous_variant	12/13		NP_001276977.1
ATL3	XM_047426725.1	c.1530A>G	p.Ser510=	synonymous_variant	13/14		XP_047282681.1
ATL3	XM_006718493.2	c.1317A>G	p.Ser439=	synonymous_variant	11/12		XP_006718556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATL3	ENST00000398868.8	c.1374A>G	p.Ser458=	synonymous_variant	12/13	1	NM_015459.5	ENSP00000381844
ATL3	ENST00000538786.1	c.1320A>G	p.Ser440=	synonymous_variant	12/13	2		ENSP00000437593	P1

Frequencies

GnomAD3 genomes AF: 0.00869 AC: 1323 AN: 152200 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00220 AC: 549 AN: 249550 Hom.: 6 AF XY: 0.00164 AC XY: 222 AN XY: 135384

Gnomad AFR exome AF: 0.0325

Gnomad AMR exome AF: 0.000985

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000991

GnomAD4 exome AF: 0.000841 AC: 1229 AN: 1461894 Hom.: 13 Cov.: 32 AF XY: 0.000679 AC XY: 494 AN XY: 727248

Gnomad4 AFR exome AF: 0.0314

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000144

Gnomad4 OTH exome AF: 0.00166

GnomAD4 genome AF: 0.00871 AC: 1327 AN: 152318 Hom.: 18 Cov.: 32 AF XY: 0.00874 AC XY: 651 AN XY: 74500

Gnomad4 AFR AF: 0.0302

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00228 Hom.: 6

Bravo AF: 0.00954

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 22, 2022	See Variant Classification Assertion Criteria. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Neuropathy, hereditary sensory, type 1F Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.77
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs17158455; hg19: chr11-63398677;