chr6-28125822-G-A

Variant names:

• chr6-28125822-G-A
• rs745465985
• NM_025231.3:c.379G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_025231.3(ZSCAN16):​c.379G>A​(p.Gly127Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000483 in 1,448,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ZSCAN16 NM_025231.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.859
• Publications: 0 publications found

Genes affected

ZSCAN16 (HGNC:20813): (zinc finger and SCAN domain containing 16) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZSCAN16-AS1 (HGNC:48982): (ZSCAN16 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05730605).
• BP6: Variant 6-28125822-G-A is Benign according to our data. Variant chr6-28125822-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2601728.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025231.3. 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
	ZSCAN16	NM_025231.3	MANE Select	c.379G>A	p.Gly127Arg	missense	Exon 2 of 4	NP_079507.1	Q9H4T2
	ZSCAN16	NM_001320555.2		c.379G>A	p.Gly127Arg	missense	Exon 2 of 4	NP_001307484.1	Q9H4T2
	ZSCAN16	NM_001320557.2		c.379G>A	p.Gly127Arg	missense	Exon 2 of 4	NP_001307486.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN16	ENST00000340487.5	TSL:1 MANE Select	c.379G>A	p.Gly127Arg	missense	Exon 2 of 4	ENSP00000366527.3	Q9H4T2
	ZSCAN16-AS1	ENST00000602810.3	TSL:1	n.574-2611C>T		intron	N/A
	ZSCAN16	ENST00000685330.1		c.379G>A	p.Gly127Arg	missense	Exon 2 of 4	ENSP00000510203.1	Q9H4T2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000132 AC: 3 AN: 227476 AF XY: 0.0000163

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: 0.0000297

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000483 AC: 7 AN: 1448520 Hom.: 0 Cov.: 30 AF XY: 0.00000556 AC XY: 4 AN XY: 719656

African (AFR) AF: 0.00 AC: 0 AN: 33154

American (AMR) AF: 0.00 AC: 0 AN: 41852

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25720

East Asian (EAS) AF: 0.00 AC: 0 AN: 39198

South Asian (SAS) AF: 0.00 AC: 0 AN: 84904

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5520

European-Non Finnish (NFE) AF: 0.00000633 AC: 7 AN: 1105288

Other (OTH) AF: 0.00 AC: 0 AN: 59960

GnomAD4 genome Cov.: 32

Alfa AF: 0.000111 Hom.: 0

ExAC AF: 0.00000825 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.16
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.90
DEOGEN2	Benign	0.099	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0072	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.055	N
PhyloP100		-0.86
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.093
Sift	Benign	0.18	T
Sift4G	Benign	0.19	T
Polyphen		0.0	B
Vest4		0.051
MutPred		0.57		Gain of solvent accessibility (P = 0.0674)
MVP		0.17
MPC		0.15
ClinPred		0.062	T
GERP RS		-7.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.12
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs745465985; hg19: chr6-28093600;