16-71849829-C-T

Variant names:

• chr16-71849829-C-T
• rs761113308
• NM_001137675.4:c.89C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001137675.4(ATXN1L):​c.89C>T​(p.Thr30Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,551,054 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: 𝑓 0.000059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: ATXN1L NM_001137675.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59
• Publications: 0 publications found

Genes affected

ATXN1L (HGNC:33279): (ataxin 1 like) Predicted to enable DNA binding activity and RNA binding activity. Predicted to be involved in several processes, including learning or memory; regulation of transcription, DNA-templated; and social behavior. Predicted to act upstream of or within several processes, including lung alveolus development; negative regulation of transcription by RNA polymerase II; and positive regulation of hematopoietic stem cell proliferation. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

IST1 (HGNC:28977): (IST1 factor associated with ESCRT-III) This gene encodes a protein with MIT-interacting motifs that interacts with components of endosomal sorting complexes required for transport (ESCRT). ESCRT functions in vesicle budding, such as that which occurs during membrane abscission in cytokinesis. There is a pseudogene for this gene on chromosome 19. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.064368755).
• BS2: High AC in GnomAd4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001137675.4. 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
	ATXN1L	NM_001137675.4	MANE Select	c.89C>T	p.Thr30Ile	missense	Exon 3 of 3	NP_001131147.1	P0C7T5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN1L	ENST00000427980.7	TSL:1 MANE Select	c.89C>T	p.Thr30Ile	missense	Exon 3 of 3	ENSP00000415822.2	P0C7T5
	ATXN1L	ENST00000683775.1		c.89C>T	p.Thr30Ile	missense	Exon 3 of 3	ENSP00000507897.1	P0C7T5
	ATXN1L	ENST00000914247.1		c.89C>T	p.Thr30Ile	missense	Exon 4 of 4	ENSP00000584306.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152114 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000195 AC: 3 AN: 153556 AF XY: 0.00

Gnomad AFR exome AF: 0.000379

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000643 AC: 9 AN: 1398940 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 689926

African (AFR) AF: 0.000127 AC: 4 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25166

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078698

Other (OTH) AF: 0.0000172 AC: 1 AN: 57980

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152114 Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5 AN XY: 74308

African (AFR) AF: 0.000193 AC: 8 AN: 41410

American (AMR) AF: 0.0000655 AC: 1 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000425 AC: 1

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	0.22
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0020	T
Eigen	Benign	0.047
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.6
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.029
Sift	Benign	0.12	T
Sift4G	Benign	0.25	T
Polyphen		0.32	B
Vest4		0.22
MVP		0.28
ClinPred		0.055	T
GERP RS		5.6
Varity_R		0.040
gMVP		0.096
Mutation Taster		=81/19	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: rs761113308; hg19: chr16-71883732;