XM_047419936.1:c.-302C>T

Variant names:

• chr7-149776495-G-A
• rs181803407
• ENST00000882861.1:c.-302C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The XM_047419936.1(ZNF467):​c.-302C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00894 in 1,318,964 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0077 (11 hom., cov: 33)
  • Exomes 𝑓: 0.0091 (76 hom.)
• Consequence: ZNF467 XM_047419936.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.206
• Publications: 4 publications found

Genes affected

ZNF467 (HGNC:23154): (zinc finger protein 467) The protein encoded by this gene is a zinc finger protein whose function has not yet been elucidated in humans. However, the mouse ortholog of this protein enhances adipocyte differentiation and suppresses osteoblast differentiation in bone marrow. The mouse protein also is a transcription factor for several genes and can help recruit histone deacetylase complexes. [provided by RefSeq, Aug 2016]

SSPOP (HGNC:21998): (SCO-spondin, pseudogene) Predicted to enable peptidase inhibitor activity. Predicted to be involved in several processes, including cell adhesion; negative regulation of catalytic activity; and regulation of peptidase activity. Predicted to be located in cytoplasm. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000293556 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026706755).
• BP6: Variant 7-149776495-G-A is Benign according to our data. Variant chr7-149776495-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2658148.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000882861.1. 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
	SSPOP	NR_163594.1		n.200G>A		non_coding_transcript_exon	Exon 2 of 103

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF467	ENST00000882861.1		c.-302C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000552920.1
	ZNF467	ENST00000882862.1		c.-566C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000552921.1
	ZNF467	ENST00000882863.1		c.-678C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000552922.1

Frequencies

GnomAD3 genomes AF: 0.00771 AC: 1173 AN: 152196 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00687

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.0206

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00873

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00996 AC: 1696 AN: 170320 AF XY: 0.00973

Gnomad AFR exome AF: 0.00167

Gnomad AMR exome AF: 0.00457

Gnomad ASJ exome AF: 0.0520

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0183

Gnomad NFE exome AF: 0.0105

Gnomad OTH exome AF: 0.0110

GnomAD4 exome AF: 0.00910 AC: 10622 AN: 1166650 Hom.: 76 Cov.: 31 AF XY: 0.00890 AC XY: 5110 AN XY: 573950

African (AFR) AF: 0.000999 AC: 25 AN: 25036

American (AMR) AF: 0.00446 AC: 135 AN: 30300

Ashkenazi Jewish (ASJ) AF: 0.0494 AC: 795 AN: 16090

East Asian (EAS) AF: 0.00 AC: 0 AN: 14030

South Asian (SAS) AF: 0.00159 AC: 123 AN: 77558

European-Finnish (FIN) AF: 0.0179 AC: 501 AN: 28042

Middle Eastern (MID) AF: 0.0103 AC: 34 AN: 3298

European-Non Finnish (NFE) AF: 0.00919 AC: 8547 AN: 930192

Other (OTH) AF: 0.0110 AC: 462 AN: 42104

GnomAD4 genome AF: 0.00768 AC: 1170 AN: 152314 Hom.: 11 Cov.: 33 AF XY: 0.00792 AC XY: 590 AN XY: 74468

African (AFR) AF: 0.00149 AC: 62 AN: 41576

American (AMR) AF: 0.00686 AC: 105 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4832

European-Finnish (FIN) AF: 0.0206 AC: 219 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00872 AC: 593 AN: 68026

Other (OTH) AF: 0.00711 AC: 15 AN: 2110

Alfa AF: 0.0103 Hom.: 10

Bravo AF: 0.00725

TwinsUK AF: 0.00701 AC: 26

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.00214 AC: 8

ESP6500EA AF: 0.0102 AC: 83

ExAC AF: 0.00605 AC: 704

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.9
DANN	Benign	0.68
DEOGEN2	Benign	0.012	T
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0027	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.21
PrimateAI	Benign	0.38	T
Sift4G	Uncertain	0.023	D
Polyphen		0.14	B
Vest4		0.14
MVP		0.095
GERP RS		0.72
Varity_R		0.088
gMVP		0.30

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: rs181803407; hg19: chr7-149473584;