NM_001170795.4:c.79A>G

Variant names:

• chr2-27212447-A-G
• rs1674616852
• NM_001170795.4:c.79A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001170795.4(ATRAID):​c.79A>G​(p.Arg27Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,411,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ATRAID NM_001170795.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.447
• Publications: 0 publications found

Genes affected

ATRAID (HGNC:24090): (all-trans retinoic acid induced differentiation factor) This gene is thought to be involved in apoptosis, and may also be involved in hematopoietic development and differentiation. The use of alternative splice sites and promotors result in multiple transcript variants encoding different isoforms.[provided by RefSeq, Dec 2009]

SLC5A6 (HGNC:11041): (solute carrier family 5 member 6) Enables biotin transmembrane transporter activity and pantothenate transmembrane transporter activity. Involved in anion transmembrane transport and transport across blood-brain barrier. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC5A6 Gene-Disease associations (from GenCC):

• neurodegeneration, infantile-onset, biotin-responsive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, PanelApp Australia
• peripheral motor neuropathy, childhood-onset, biotin-responsive

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• inherited neurodegenerative disorder

  Inheritance: AR Classification: MODERATE Submitted by: Illumina

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15843579).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170795.4. 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
	ATRAID	NM_001170795.4	MANE Select	c.79A>G	p.Arg27Gly	missense	Exon 1 of 7	NP_001164266.1	Q6UW56-1
	ATRAID	NM_016085.5		c.-236A>G		5_prime_UTR	Exon 1 of 7	NP_057169.2
	SLC5A6	NM_021095.4	MANE Select	c.-635T>C		upstream_gene	N/A	NP_066918.2	Q9Y289

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRAID	ENST00000380171.9	TSL:1 MANE Select	c.79A>G	p.Arg27Gly	missense	Exon 1 of 7	ENSP00000369518.4	Q6UW56-1
	ATRAID	ENST00000405489.7	TSL:1	c.-236A>G		5_prime_UTR	Exon 1 of 7	ENSP00000384033.3	Q6UW56-2
	ATRAID	ENST00000892973.1		c.79A>G	p.Arg27Gly	missense	Exon 1 of 7	ENSP00000563032.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.0000113 AC: 16 AN: 1411086 Hom.: 0 Cov.: 77 AF XY: 0.00000860 AC XY: 6 AN XY: 697756

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 37808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.0000275 AC: 1 AN: 36334

South Asian (SAS) AF: 0.00 AC: 0 AN: 79706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.0000110 AC: 12 AN: 1087014

Other (OTH) AF: 0.0000513 AC: 3 AN: 58486

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.45
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.13
Sift	Benign	0.16	T
Sift4G	Uncertain	0.0080	D
Polyphen		0.98	D
Vest4		0.14
MutPred		0.29		Loss of helix (P = 0.028)
MVP		0.48
MPC		0.082
ClinPred		0.69	D
GERP RS		1.1
PromoterAI		-0.0041	Neutral
Varity_R		0.10
gMVP		0.45
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1674616852; hg19: chr2-27435315;