rs542176148

Variant names:

• chr16-10430733-T-C
• rs542176148
• NM_001393719.1:c.113T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001393719.1(ATF7IP2):​c.113T>C​(p.Leu38Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,614,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: ATF7IP2 NM_001393719.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.684
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.116484284).

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.113T>C	p.Leu38Pro	missense	Exon 5 of 14	NP_001380648.1	Q5U623-1
	ATF7IP2	NM_001352120.2		c.113T>C	p.Leu38Pro	missense	Exon 4 of 13	NP_001339049.1	Q5U623-1
	ATF7IP2	NM_024997.5		c.113T>C	p.Leu38Pro	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.113T>C	p.Leu38Pro	missense	Exon 5 of 14	ENSP00000457731.2	Q5U623-1
	ATF7IP2	ENST00000356427.2	TSL:1	c.113T>C	p.Leu38Pro	missense	Exon 1 of 10	ENSP00000348799.2	Q5U623-1
	ATF7IP2	ENST00000396560.6	TSL:1	c.113T>C	p.Leu38Pro	missense	Exon 3 of 12	ENSP00000379808.2	Q5U623-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251362 AF XY: 0.0000147

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000150 AC: 22 AN: 1461848 Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11 AN XY: 727228

African (AFR) AF: 0.000418 AC: 14 AN: 33480

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: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111986

Other (OTH) AF: 0.0000993 AC: 6 AN: 60394

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74476

African (AFR) AF: 0.00 AC: 0 AN: 41566

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.20
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.082
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.68
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.17
Sift	Benign	0.18	T
Sift4G	Benign	0.28	T
Polyphen		0.36	B
Vest4		0.47
MutPred		0.24		Loss of stability (P = 0.0024)
MVP		0.83
MPC		0.014
ClinPred		0.34	T
GERP RS		3.0
PromoterAI		0.0040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.51
gMVP		0.33
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs542176148; hg19: chr16-10524590;