16-10430856-C-A

Variant names:

• chr16-10430856-C-A
• rs762048546
• NM_001393719.1:c.236C>A

Variant summary

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

The NM_001393719.1(ATF7IP2):​c.236C>A​(p.Ser79Tyr) 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. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S79C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATF7IP2 NM_001393719.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.599
• Publications: 0 publications found

Genes affected

ATF7IP2 (HGNC:20397): (activating transcription factor 7 interacting protein 2) Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.13671562).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393719.1. 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
	ATF7IP2	NM_001393719.1	MANE Select	c.236C>A	p.Ser79Tyr	missense	Exon 5 of 14	NP_001380648.1	Q5U623-1
	ATF7IP2	NM_001352120.2		c.236C>A	p.Ser79Tyr	missense	Exon 4 of 13	NP_001339049.1	Q5U623-1
	ATF7IP2	NM_024997.5		c.236C>A	p.Ser79Tyr	missense	Exon 3 of 12	NP_079273.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF7IP2	ENST00000562102.6	TSL:4 MANE Select	c.236C>A	p.Ser79Tyr	missense	Exon 5 of 14	ENSP00000457731.2	Q5U623-1
	ATF7IP2	ENST00000356427.2	TSL:1	c.236C>A	p.Ser79Tyr	missense	Exon 1 of 10	ENSP00000348799.2	Q5U623-1
	ATF7IP2	ENST00000396560.6	TSL:1	c.236C>A	p.Ser79Tyr	missense	Exon 3 of 12	ENSP00000379808.2	Q5U623-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T
Eigen	Benign	0.093
Eigen_PC	Benign	-0.041
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.60
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.15		Loss of methylation at K81 (P = 0.0633)
MVP		0.20
MPC		0.057
ClinPred		0.75	D
GERP RS		4.3
PromoterAI		0.012	Neutral
Varity_R		0.18
gMVP		0.12

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: rs762048546; hg19: chr16-10524713;