2-67397563-T-G

Variant names:

• chr2-67397563-T-G
• rs201688163
• NM_019002.4:c.115T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019002.4(ETAA1):​c.115T>G​(p.Ser39Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,416,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S39P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ETAA1 NM_019002.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133
• Publications: 0 publications found

Genes affected

ETAA1 (HGNC:24648): (ETAA1 activator of ATR kinase) Enables protein serine/threonine kinase activator activity. Involved in several processes, including positive regulation of protein serine/threonine kinase activity; regulation of DNA damage checkpoint; and replication fork processing. Located in cytosol; nuclear replication fork; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LINC01829 (HGNC:52635): (long intergenic non-protein coding RNA 1829)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04876691).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019002.4. 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
	ETAA1	NM_019002.4	MANE Select	c.115T>G	p.Ser39Ala	missense	Exon 1 of 6	NP_061875.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETAA1	ENST00000272342.6	TSL:1 MANE Select	c.115T>G	p.Ser39Ala	missense	Exon 1 of 6	ENSP00000272342.5	Q9NY74
	ETAA1	ENST00000925952.1		c.115T>G	p.Ser39Ala	missense	Exon 1 of 6	ENSP00000596011.1
	ETAA1	ENST00000925951.1		c.115T>G	p.Ser39Ala	missense	Exon 1 of 6	ENSP00000596010.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1416922 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 700566

African (AFR) AF: 0.0000309 AC: 1 AN: 32322

American (AMR) AF: 0.00 AC: 0 AN: 38502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25392

East Asian (EAS) AF: 0.00 AC: 0 AN: 37250

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5196

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1089442

Other (OTH) AF: 0.00 AC: 0 AN: 58602

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.69
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.83	L
PhyloP100		0.13
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.023
Sift	Benign	0.58	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.14
MutPred		0.19		Loss of phosphorylation at S39 (P = 0.0042)
MVP		0.13
MPC		0.039
ClinPred		0.036	T
GERP RS		-0.91
PromoterAI		-0.071	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.038
gMVP		0.033
Mutation Taster		=100/0	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: rs201688163; hg19: chr2-67624695;