NM_001144950.2:c.3930C>T

Variant names:

• chr19-55518206-C-T
• rs754825722
• NM_001144950.2:c.3930C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001144950.2(SSC5D):​c.3930C>T​(p.Thr1310Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 21)
  • Exomes 𝑓: 0.00078 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SSC5D NM_001144950.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0140
• Publications: 1 publications found

Genes affected

SSC5D (HGNC:26641): (scavenger receptor cysteine rich family member with 5 domains) Predicted to enable fibronectin binding activity; laminin binding activity; and scavenger receptor activity. Predicted to be involved in defense response; detection of bacterial lipoprotein; and negative regulation of interleukin-8 production. Predicted to act upstream of or within regulation of interleukin-8 production. Predicted to be located in collagen-containing extracellular matrix. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000300360 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-55518206-C-T is Benign according to our data. Variant chr19-55518206-C-T is described in ClinVar as Benign. ClinVar VariationId is 403488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.014 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144950.2. 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
	SSC5D	NM_001144950.2	MANE Select	c.3930C>T	p.Thr1310Thr	synonymous	Exon 14 of 14	NP_001138422.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSC5D	ENST00000389623.11	TSL:1 MANE Select	c.3930C>T	p.Thr1310Thr	synonymous	Exon 14 of 14	ENSP00000374274.4
	ENSG00000300360	ENST00000771167.1		n.231+2566G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00207 AC: 228 AN: 110394 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00764

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00198

Gnomad ASJ AF: 0.00104

Gnomad EAS AF: 0.000993

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000637

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000433

Gnomad OTH AF: 0.00330

GnomAD2 exomes AF: 0.00155 AC: 196 AN: 126818 AF XY: 0.00123

Gnomad AFR exome AF: 0.0107

Gnomad AMR exome AF: 0.00423

Gnomad ASJ exome AF: 0.00128

Gnomad EAS exome AF: 0.00157

Gnomad FIN exome AF: 0.00123

Gnomad NFE exome AF: 0.000619

Gnomad OTH exome AF: 0.00109

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000780 AC: 1025 AN: 1314156 Hom.: 0 Cov.: 75 AF XY: 0.000709 AC XY: 459 AN XY: 647764

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0154 AC: 418 AN: 27210

American (AMR) AF: 0.00228 AC: 68 AN: 29890

Ashkenazi Jewish (ASJ) AF: 0.000842 AC: 19 AN: 22578

East Asian (EAS) AF: 0.000500 AC: 15 AN: 30012

South Asian (SAS) AF: 0.0000921 AC: 7 AN: 76018

European-Finnish (FIN) AF: 0.000202 AC: 9 AN: 44518

Middle Eastern (MID) AF: 0.00130 AC: 7 AN: 5392

European-Non Finnish (NFE) AF: 0.000392 AC: 402 AN: 1025238

Other (OTH) AF: 0.00150 AC: 80 AN: 53300

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00208 AC: 230 AN: 110452 Hom.: 0 Cov.: 21 AF XY: 0.00222 AC XY: 119 AN XY: 53676

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00771 AC: 169 AN: 21922

American (AMR) AF: 0.00197 AC: 20 AN: 10136

Ashkenazi Jewish (ASJ) AF: 0.00104 AC: 3 AN: 2886

East Asian (EAS) AF: 0.000993 AC: 3 AN: 3020

South Asian (SAS) AF: 0.00 AC: 0 AN: 4302

European-Finnish (FIN) AF: 0.000637 AC: 5 AN: 7844

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 220

European-Non Finnish (NFE) AF: 0.000433 AC: 25 AN: 57738

Other (OTH) AF: 0.00325 AC: 5 AN: 1538

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0373 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.99
DANN	Benign	0.41
PhyloP100		0.014
Mutation Taster		=100/0	polymorphism

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: rs754825722; hg19: chr19-56029573;