10-30914163-T-C

Variant names:

• chr10-30914163-T-C
• rs1038972
• NM_001143768.2:c.-114-5148A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143768.2(ZNF438):​c.-114-5148A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.912 in 152,136 control chromosomes in the GnomAD database, including 63,486 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.91 (63486 hom., cov: 32)
• Consequence: ZNF438 NM_001143768.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987
• Publications: 3 publications found

Genes affected

ZNF438 (HGNC:21029): (zinc finger protein 438) Enables DNA-binding transcription factor activity. Involved in negative regulation of transcription, DNA-templated. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143768.2. 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
	ZNF438	NM_001143768.2	MANE Select	c.-114-5148A>G		intron	N/A	NP_001137240.1	Q7Z4V0-1
	ZNF438	NM_001143766.2		c.-114-5148A>G		intron	N/A	NP_001137238.1	Q7Z4V0-1
	ZNF438	NM_001143767.2		c.-114-5148A>G		intron	N/A	NP_001137239.1	Q7Z4V0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF438	ENST00000436087.7	TSL:5 MANE Select	c.-114-5148A>G		intron	N/A	ENSP00000406934.2	Q7Z4V0-1
	ZNF438	ENST00000361310.7	TSL:1	c.-195-3723A>G		intron	N/A	ENSP00000354663.3	Q7Z4V0-1
	ZNF438	ENST00000331737.10	TSL:1	c.-324-3723A>G		intron	N/A	ENSP00000333571.6	Q7Z4V0-2

Frequencies

GnomAD3 genomes AF: 0.912 AC: 138657 AN: 152018 Hom.: 63430 Cov.: 32

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.949

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.904

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.912 AC: 138770 AN: 152136 Hom.: 63486 Cov.: 32 AF XY: 0.913 AC XY: 67915 AN XY: 74362

African (AFR) AF: 0.977 AC: 40548 AN: 41516

American (AMR) AF: 0.919 AC: 14023 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2962 AN: 3472

East Asian (EAS) AF: 0.956 AC: 4942 AN: 5170

South Asian (SAS) AF: 0.949 AC: 4575 AN: 4822

European-Finnish (FIN) AF: 0.849 AC: 8990 AN: 10590

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.878 AC: 59716 AN: 67988

Other (OTH) AF: 0.902 AC: 1904 AN: 2110

Alfa AF: 0.886 Hom.: 87066

Bravo AF: 0.920

Asia WGS AF: 0.946 AC: 3289 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.50
PhyloP100		-0.99
Mutation Taster		=100/0	polymorphism (auto)

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: rs1038972; hg19: chr10-31203092;