2-27212295-G-A

Variant names:

• chr2-27212295-G-A
• rs762557057
• NM_001170795.4:c.-74G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001170795.4(ATRAID):​c.-74G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATRAID NM_001170795.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062157094).

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.-74G>A		5_prime_UTR	Exon 1 of 7	NP_001164266.1	Q6UW56-1
	SLC5A6	NM_021095.4	MANE Select	c.-483C>T		upstream_gene	N/A	NP_066918.2	Q9Y289
	ATRAID	NM_016085.5		c.-388G>A		upstream_gene	N/A	NP_057169.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRAID	ENST00000380171.9	TSL:1 MANE Select	c.-74G>A		5_prime_UTR	Exon 1 of 7	ENSP00000369518.4	Q6UW56-1
	SLC5A6	ENST00000892748.1		c.-208+334C>T		intron	N/A	ENSP00000562807.1
	SLC5A6	ENST00000432106.5	TSL:3	c.-208+537C>T		intron	N/A	ENSP00000411536.1	E7ENG0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.0
DANN	Benign	0.90
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.41
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.018
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.13
MutPred		0.26		Loss of methylation at R31 (P = 0.0068)
MVP		0.17
MPC		0.092
ClinPred		0.14	T
GERP RS		-7.8
PromoterAI		-0.049	Neutral
gMVP		0.30
Mutation Taster		=100/0	polymorphism

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: rs762557057; hg19: chr2-27435163; COSMIC: COSV60160658; COSMIC: COSV60160658;