chr7-3962677-C-G

Position:

• chr7-3962677-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_152744.4(SDK1):​c.1255C>G​(p.Gln419Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,612,602 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (22 hom., cov: 33)
  • Exomes 𝑓: 0.012 (151 hom.)
• Consequence: SDK1 NM_152744.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.48

Genes affected

SDK1 (HGNC:19307): (sidekick cell adhesion molecule 1) The protein encoded by this gene is a member of the immunoglobulin superfamily. The protein contains six immunoglobulin-like domains and thirteen fibronectin type III domains. Fibronectin type III domains are present in both extracellular and intracellular proteins and tandem repeats are known to contain binding sites for DNA, heparin and the cell surface. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0108831525).
• BP6: Variant 7-3962677-C-G is Benign according to our data. Variant chr7-3962677-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 445721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0106 (1618/152342) while in subpopulation AMR AF= 0.034 (521/15302). AF 95% confidence interval is 0.0316. There are 22 homozygotes in gnomad4. There are 803 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDK1	NM_152744.4	c.1255C>G	p.Gln419Glu	missense_variant	9/45	ENST00000404826.7	NP_689957.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDK1	ENST00000404826.7	c.1255C>G	p.Gln419Glu	missense_variant	9/45	1	NM_152744.4	ENSP00000385899.2
SDK1	ENST00000389531.7	c.1255C>G	p.Gln419Glu	missense_variant	9/44	5		ENSP00000374182.3

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1622 AN: 152224 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00232

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.0106 AC: 2637 AN: 249490 Hom.: 35 AF XY: 0.0101 AC XY: 1357 AN XY: 134796

Gnomad AFR exome AF: 0.00167

Gnomad AMR exome AF: 0.0253

Gnomad ASJ exome AF: 0.00413

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000328

Gnomad FIN exome AF: 0.0118

Gnomad NFE exome AF: 0.0121

Gnomad OTH exome AF: 0.0121

GnomAD4 exome AF: 0.0120 AC: 17553 AN: 1460260 Hom.: 151 Cov.: 31 AF XY: 0.0114 AC XY: 8272 AN XY: 726354

Gnomad4 AFR exome AF: 0.00191

Gnomad4 AMR exome AF: 0.0265

Gnomad4 ASJ exome AF: 0.00323

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000348

Gnomad4 FIN exome AF: 0.0120

Gnomad4 NFE exome AF: 0.0134

Gnomad4 OTH exome AF: 0.0109

GnomAD4 genome AF: 0.0106 AC: 1618 AN: 152342 Hom.: 22 Cov.: 33 AF XY: 0.0108 AC XY: 803 AN XY: 74486

Gnomad4 AFR AF: 0.00231

Gnomad4 AMR AF: 0.0340

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0103

Gnomad4 NFE AF: 0.0126

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.0110 Hom.: 6

Bravo AF: 0.0117

TwinsUK AF: 0.0151 AC: 56

ALSPAC AF: 0.0143 AC: 55

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.0109 AC: 94

ExAC AF: 0.00950 AC: 1153

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0115

EpiControl AF: 0.0107

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 20, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.58
DEOGEN2	Benign	0.026	T;T;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.68	T;T;T
MetaRNN	Benign	0.011	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.21	N;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.16	N;N;.
REVEL	Benign	0.13
Sift	Benign	0.81	T;T;.
Sift4G	Benign	0.89	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.24
MPC		0.074
ClinPred		0.0057	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.091
gMVP		0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs150503747; hg19: chr7-4002309;