NM_001385016.1:c.1965G>T

Variant names:

• chr15-52608949-C-A
• rs764861894
• NM_001385016.1:c.1965G>T

Variant summary

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

The NM_001385016.1(ATOSA):​c.1965G>T​(p.Lys655Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,994 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ATOSA NM_001385016.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337
• Publications: 0 publications found

Genes affected

ATOSA (HGNC:25609): (atos homolog A)

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=0.13108158).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385016.1. 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
	ATOSA	NM_001385016.1	MANE Select	c.1965G>T	p.Lys655Asn	missense	Exon 6 of 13	NP_001371945.1	Q32MH5-1
	ATOSA	NM_001286495.2		c.1986G>T	p.Lys662Asn	missense	Exon 5 of 12	NP_001273424.1	Q32MH5-3
	ATOSA	NM_001385019.1		c.1986G>T	p.Lys662Asn	missense	Exon 6 of 13	NP_001371948.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATOSA	ENST00000619572.5	TSL:1 MANE Select	c.1965G>T	p.Lys655Asn	missense	Exon 6 of 13	ENSP00000484641.1	Q32MH5-1
	ATOSA	ENST00000261844.11	TSL:1	c.1965G>T	p.Lys655Asn	missense	Exon 6 of 13	ENSP00000261844.7	Q32MH5-1
	ATOSA	ENST00000399202.8	TSL:1	c.1701G>T	p.Lys567Asn	missense	Exon 5 of 11	ENSP00000382153.4	H0Y3Q9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000408 AC: 1 AN: 245072 AF XY: 0.00000753

Gnomad AFR exome AF: 0.00

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: 0.00000898

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1456994 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724632

African (AFR) AF: 0.00 AC: 0 AN: 33140

American (AMR) AF: 0.00 AC: 0 AN: 44038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.00 AC: 0 AN: 39572

South Asian (SAS) AF: 0.00 AC: 0 AN: 85028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110504

Other (OTH) AF: 0.00 AC: 0 AN: 60186

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.34
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.14
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.059	T
Polyphen		0.99	D
Vest4		0.19
MutPred		0.29		Loss of methylation at K655 (P = 0.0203)
MVP		0.13
MPC		0.47
ClinPred		0.66	D
GERP RS		-3.7
Varity_R		0.17
gMVP		0.22
Mutation Taster		=91/9	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: rs764861894; hg19: chr15-52901146;