NM_020725.2:c.2104A>C

Variant names:

• chr7-105614230-T-G
• NM_020725.2:c.2104A>C

Variant summary

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

The NM_020725.2(ATXN7L1):​c.2104A>C​(p.Asn702His) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATXN7L1 NM_020725.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.10
• Publications: 0 publications found

Genes affected

ATXN7L1 (HGNC:22210): (ataxin 7 like 1)

ENSG00000295921 (HGNC:):

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=0.1628724).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020725.2. 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
	ATXN7L1	NM_020725.2	MANE Select	c.2104A>C	p.Asn702His	missense	Exon 10 of 12	NP_065776.1	Q9ULK2-1
	ATXN7L1	NM_001385596.1		c.2104A>C	p.Asn702His	missense	Exon 10 of 12	NP_001372525.1
	ATXN7L1	NM_138495.2		c.1732A>C	p.Asn578His	missense	Exon 8 of 10	NP_612504.1	Q9ULK2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN7L1	ENST00000419735.8	TSL:1 MANE Select	c.2104A>C	p.Asn702His	missense	Exon 10 of 12	ENSP00000410759.3	Q9ULK2-1
	ATXN7L1	ENST00000484475.5	TSL:1	c.1207A>C	p.Asn403His	missense	Exon 4 of 4	ENSP00000418900.1	H0Y8A2
	ATXN7L1	ENST00000474433.5	TSL:1	n.*1679A>C		non_coding_transcript_exon	Exon 9 of 9	ENSP00000420483.1	F8WDE7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.076
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0093	T
Eigen	Benign	0.057
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.1
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.035
Sift	Benign	0.065	T
Sift4G	Uncertain	0.056	T
Polyphen		0.38	B
Vest4		0.48
MutPred		0.25		Gain of sheet (P = 0.0477)
MVP		0.50
MPC		0.72
ClinPred		0.53	D
GERP RS		4.3
Varity_R		0.099
gMVP		0.36
Mutation Taster		=86/14	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

hg19: chr7-105254677;