6-85625246-C-G

Variant names:

• chr6-85625246-C-G
• rs16876385
• NM_006372.5:c.667-1134G>C

Variant summary

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

The NM_006372.5(SYNCRIP):​c.667-1134G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 152,122 control chromosomes in the GnomAD database, including 831 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 0.082 (831 hom., cov: 31)
• Consequence: SYNCRIP NM_006372.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.503
• Publications: 1 publications found

Genes affected

SYNCRIP (HGNC:16918): (synaptotagmin binding cytoplasmic RNA interacting protein) This gene encodes a member of the cellular heterogeneous nuclear ribonucleoprotein (hnRNP) family. hnRNPs are RNA binding proteins that complex with heterogeneous nuclear RNA (hnRNA) and regulate alternative splicing, polyadenylation, and other aspects of mRNA metabolism and transport. The encoded protein plays a role in multiple aspects of mRNA maturation and is associated with several multiprotein complexes including the apoB RNA editing-complex and survival of motor neurons (SMN) complex. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 20. [provided by RefSeq, Dec 2011]

SYNCRIP Gene-Disease associations (from GenCC):

• SYNCRIP-related neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ENSG00000271793 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNCRIP	NM_006372.5	c.667-1134G>C		intron_variant	Intron 6 of 10	ENST00000369622.8	NP_006363.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNCRIP	ENST00000369622.8	c.667-1134G>C		intron_variant	Intron 6 of 10	1	NM_006372.5	ENSP00000358635.3
ENSG00000271793	ENST00000682083.1	n.667-1134G>C		intron_variant	Intron 6 of 39			ENSP00000506859.1

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12464 AN: 152004 Hom.: 833 Cov.: 31

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0217

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0304

Gnomad OTH AF: 0.0924

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

GnomAD4 genome AF: 0.0820 AC: 12473 AN: 152122 Hom.: 831 Cov.: 31 AF XY: 0.0855 AC XY: 6360 AN XY: 74360

African (AFR) AF: 0.146 AC: 6070 AN: 41492

American (AMR) AF: 0.102 AC: 1562 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0934 AC: 324 AN: 3470

East Asian (EAS) AF: 0.217 AC: 1124 AN: 5172

South Asian (SAS) AF: 0.177 AC: 853 AN: 4816

European-Finnish (FIN) AF: 0.0217 AC: 230 AN: 10592

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0304 AC: 2070 AN: 68004

Other (OTH) AF: 0.0910 AC: 192 AN: 2110

Alfa AF: 0.0126 Hom.: 7

Bravo AF: 0.0894

Asia WGS AF: 0.187 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.39
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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: rs16876385; hg19: chr6-86334964;