16-71850116-C-T

Variant names:

• chr16-71850116-C-T
• rs1743712295
• NM_001137675.4:c.376C>T

Variant summary

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

The NM_001137675.4(ATXN1L):​c.376C>T​(p.Pro126Ser) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P126T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATXN1L NM_001137675.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.69
• 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: 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=0.16021284).

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.376C>T	p.Pro126Ser	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.376C>T	p.Pro126Ser	missense	Exon 3 of 3	ENSP00000415822.2	P0C7T5
	ATXN1L	ENST00000683775.1		c.376C>T	p.Pro126Ser	missense	Exon 3 of 3	ENSP00000507897.1	P0C7T5
	ATXN1L	ENST00000914247.1		c.376C>T	p.Pro126Ser	missense	Exon 4 of 4	ENSP00000584306.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.084
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0094	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.7
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.077
Sift	Benign	0.055	T
Sift4G	Benign	0.10	T
Polyphen		0.66	P
Vest4		0.14
MutPred		0.47		Loss of catalytic residue at P125 (P = 0.012)
MVP		0.37
ClinPred		0.39	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.075
gMVP		0.55

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: rs1743712295; hg19: chr16-71884019;