16-10430826-C-T

Variant names:

• chr16-10430826-C-T
• rs373800091
• NM_001393719.1:c.206C>T

Variant summary

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

The NM_001393719.1(ATF7IP2):​c.206C>T​(p.Pro69Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P69H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ATF7IP2 NM_001393719.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• 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: 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=0.057599574).

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.206C>T	p.Pro69Leu	missense	Exon 5 of 14	NP_001380648.1	Q5U623-1
	ATF7IP2	NM_001352120.2		c.206C>T	p.Pro69Leu	missense	Exon 4 of 13	NP_001339049.1	Q5U623-1
	ATF7IP2	NM_024997.5		c.206C>T	p.Pro69Leu	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.206C>T	p.Pro69Leu	missense	Exon 5 of 14	ENSP00000457731.2	Q5U623-1
	ATF7IP2	ENST00000356427.2	TSL:1	c.206C>T	p.Pro69Leu	missense	Exon 1 of 10	ENSP00000348799.2	Q5U623-1
	ATF7IP2	ENST00000396560.6	TSL:1	c.206C>T	p.Pro69Leu	missense	Exon 3 of 12	ENSP00000379808.2	Q5U623-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461762 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727182

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111912

Other (OTH) AF: 0.00 AC: 0 AN: 60390

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.0080
DANN	Benign	0.54
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.2
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.020
Sift	Benign	0.15	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.045
MutPred		0.10		Loss of glycosylation at P69 (P = 0.0693)
MVP		0.043
MPC		0.0096
ClinPred		0.17	T
GERP RS		-7.0
PromoterAI		-0.0085	Neutral
Varity_R		0.023
gMVP		0.038
Mutation Taster		=93/7	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: rs373800091; hg19: chr16-10524683;