rs771464722

Variant names:

• chr8-78678596-A-C
• rs771464722
• NM_016010.3:c.127A>C

Your query was ambiguous. Multiple possible variants found:

• chr8-78678596-A-C
• chr8-78678596-A-G

Variant summary

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

The NM_016010.3(ZC2HC1A):​c.127A>C​(p.Thr43Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,459,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. T43A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZC2HC1A NM_016010.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.848
• Publications: 0 publications found

Genes affected

ZC2HC1A (HGNC:24277): (zinc finger C2HC-type containing 1A) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

IL7 (HGNC:6023): (interleukin 7) The protein encoded by this gene is a cytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. IL7 is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRB) during early T cell development. This cytokine can be produced locally by intestinal epithelial and epithelial goblet cells, and may serve as a regulatory factor for intestinal mucosal lymphocytes. IL7 plays an essential role in lymphoid cell survival, and in the maintenance of naive and memory T cells. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their presence in normal tissues has not been confirmed. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can be a potent inducer of proinflammatory cytokines and chemokines which may defend against the infection, but may also mediate destructive lung injury. Elevated serum IL7 levels, together with several other circulating cytokines and chemokines, has been found to be associated with the severity of Coronavirus Disease 19 (COVID-19). [provided by RefSeq, Jul 2020]

IL7 Gene-Disease associations (from GenCC):

• epidermodysplasia verruciformis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• epidermodysplasia verruciformis, susceptibility to, 5

  Inheritance: AR Classification: LIMITED Submitted by: G2P

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=0.12289983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC2HC1A	NM_016010.3	c.127A>C	p.Thr43Pro	missense_variant	Exon 3 of 9	ENST00000263849.9	NP_057094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC2HC1A	ENST00000263849.9	c.127A>C	p.Thr43Pro	missense_variant	Exon 3 of 9	1	NM_016010.3	ENSP00000263849.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000800 AC: 2 AN: 249892 AF XY: 0.00000740

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: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1459966 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726274

African (AFR) AF: 0.00 AC: 0 AN: 33304

American (AMR) AF: 0.00 AC: 0 AN: 44456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.00 AC: 0 AN: 85902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111224

Other (OTH) AF: 0.00 AC: 0 AN: 60292

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.012
Eigen_PC	Benign	-0.045
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.85
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.11
Sift	Benign	0.040	D
Sift4G	Benign	0.18	T
Polyphen		0.94	P
Vest4		0.31
MutPred		0.25		Loss of phosphorylation at T43 (P = 0.0183);
MVP		0.082
MPC		0.23
ClinPred		0.65	D
GERP RS		3.4
Varity_R		0.22
gMVP		0.42
Mutation Taster		=92/8	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: rs771464722; hg19: chr8-79590831;