NM_152592.6:c.-14-14400C>G

Variant names:

• chr14-95490235-G-C
• rs734313
• NM_152592.6:c.-14-14400C>G

Variant summary

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

The NM_152592.6(SYNE3):​c.-14-14400C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,196 control chromosomes in the GnomAD database, including 31,290 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 0.63 (31290 hom., cov: 34)
• Consequence: SYNE3 NM_152592.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 4 publications found

Genes affected

SYNE3 (HGNC:19861): (spectrin repeat containing nuclear envelope family member 3) Enables actin filament binding activity and cytoskeleton-nuclear membrane anchor activity. Involved in cytoskeleton organization; establishment of protein localization to membrane; and regulation of cell shape. Located in nuclear membrane. Part of meiotic nuclear membrane microtubule tethering complex. Biomarker of Huntington's disease. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152592.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE3	NM_152592.6	MANE Select	c.-14-14400C>G		intron	N/A	NP_689805.3
	SYNE3	NM_001363692.2		c.-14-14400C>G		intron	N/A	NP_001350621.1
	SYNE3	NM_001384281.1		c.-14-14400C>G		intron	N/A	NP_001371210.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE3	ENST00000682763.1	MANE Select	c.-14-14400C>G		intron	N/A	ENSP00000507501.1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96336 AN: 152078 Hom.: 31247 Cov.: 34

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.634 AC: 96435 AN: 152196 Hom.: 31290 Cov.: 34 AF XY: 0.636 AC XY: 47322 AN XY: 74422

African (AFR) AF: 0.773 AC: 32111 AN: 41540

American (AMR) AF: 0.623 AC: 9521 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2123 AN: 3472

East Asian (EAS) AF: 0.706 AC: 3652 AN: 5170

South Asian (SAS) AF: 0.650 AC: 3135 AN: 4822

European-Finnish (FIN) AF: 0.566 AC: 5986 AN: 10582

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37850 AN: 68000

Other (OTH) AF: 0.648 AC: 1369 AN: 2112

Alfa AF: 0.596 Hom.: 3460

Bravo AF: 0.643

Asia WGS AF: 0.662 AC: 2304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.69
PhyloP100		-0.063

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs734313; hg19: chr14-95956572;