XM_047425335.1:c.-145G>A

Variant names:

• chr10-102502871-G-A
• rs2296590
• XM_047425335.1:c.-145G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047425335.1(SUFU):​c.-145G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,118 control chromosomes in the GnomAD database, including 9,539 homozygotes. 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: 𝑓 0.35 (9539 hom., cov: 33)
• Consequence: SUFU XM_047425335.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231
• Publications: 19 publications found

Genes affected

SUFU (HGNC:16466): (SUFU negative regulator of hedgehog signaling) The Hedgehog signaling pathway plays an important role in early human development. The pathway is a signaling cascade that plays a role in pattern formation and cellular proliferation during development. This gene encodes a negative regulator of the hedgehog signaling pathway. Defects in this gene are a cause of medulloblastoma. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

ACTR1A (HGNC:167): (actin related protein 1A) This gene encodes a 42.6 kD subunit of dynactin, a macromolecular complex consisting of 10-11 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein. It is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis. This subunit is present in 8-13 copies per dynactin molecule, and is the most abundant molecule in the dynactin complex. It is an actin-related protein, and is approximately 60% identical at the amino acid level to conventional actin. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369905.9. 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
	ACTR1A	NM_005736.4	MANE Select	c.-224C>T		upstream_gene	N/A	NP_005727.1	P61163

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTR1A	ENST00000369905.9	TSL:1 MANE Select	c.-224C>T		upstream_gene	N/A	ENSP00000358921.4	P61163
	ACTR1A	ENST00000972053.1		c.-224C>T		upstream_gene	N/A	ENSP00000642112.1
	ACTR1A	ENST00000900302.1		c.-224C>T		upstream_gene	N/A	ENSP00000570361.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53376 AN: 152000 Hom.: 9527 Cov.: 33

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.314

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.351 AC: 53411 AN: 152118 Hom.: 9539 Cov.: 33 AF XY: 0.352 AC XY: 26199 AN XY: 74372

African (AFR) AF: 0.391 AC: 16214 AN: 41500

American (AMR) AF: 0.372 AC: 5692 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3470

East Asian (EAS) AF: 0.259 AC: 1339 AN: 5176

South Asian (SAS) AF: 0.286 AC: 1380 AN: 4828

European-Finnish (FIN) AF: 0.381 AC: 4033 AN: 10576

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22774 AN: 67972

Other (OTH) AF: 0.310 AC: 655 AN: 2110

Alfa AF: 0.341 Hom.: 25014

Bravo AF: 0.354

Asia WGS AF: 0.295 AC: 1028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.8
DANN	Benign	0.80
PhyloP100		0.23
PromoterAI		-0.059	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2296590; hg19: chr10-104262628;