NM_001370215.1:c.257C>G

Variant names:

• chr19-56621364-C-G
• rs373161176
• NM_001370215.1:c.257C>G

Variant summary

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

The NM_001370215.1(ZNF71):​c.257C>G​(p.Thr86Arg) 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. 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. T86M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF71 NM_001370215.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.83
• Publications: 0 publications found

Genes affected

ZNF71 (HGNC:13141): (zinc finger protein 71) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000293626 (HGNC:):

ZIM2-AS1 (HGNC:51304): (ZIM2 antisense RNA 1)

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=0.06968379).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370215.1. 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
	ZNF71	NM_001370215.1	MANE Select	c.257C>G	p.Thr86Arg	missense	Exon 4 of 4	NP_001357144.1	M0R0C0
	ZNF71	NM_001370214.1		c.77C>G	p.Thr26Arg	missense	Exon 3 of 3	NP_001357143.1	Q9NQZ8
	ZNF71	NM_021216.5		c.77C>G	p.Thr26Arg	missense	Exon 3 of 3	NP_067039.1	Q9NQZ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF71	ENST00000599599.7	TSL:2 MANE Select	c.257C>G	p.Thr86Arg	missense	Exon 4 of 4	ENSP00000471138.2	M0R0C0
	ZNF71	ENST00000328070.10	TSL:1	c.77C>G	p.Thr26Arg	missense	Exon 3 of 3	ENSP00000328245.5	Q9NQZ8
	ENSG00000293626	ENST00000716550.1		n.160+7426C>G		intron	N/A	ENSP00000520562.1	A0ABB0MV33

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000433 AC: 1 AN: 231184 AF XY: 0.00000803

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: 0.00000950

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.017
DANN	Benign	0.93
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.55	N
PhyloP100		-4.8
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.027
Sift	Benign	0.46	T
Sift4G	Benign	0.37	T
Polyphen		0.0020	B
Vest4		0.15
MutPred		0.25		Loss of glycosylation at T26 (P = 0.0169)
MVP		0.014
MPC		0.42
ClinPred		0.049	T
GERP RS		-2.2
Varity_R		0.055
gMVP		0.081
Mutation Taster		=100/0	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: rs373161176; hg19: chr19-57132732;