2-32640454-G-C

Variant names:

• chr2-32640454-G-C
• rs1031261
• NM_017735.5:c.537+44G>C

Variant summary

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

The NM_017735.5(TTC27):​c.537+44G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,592,104 control chromosomes in the GnomAD database, including 18,220 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 0.14 (1615 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16605 hom.)
• Consequence: TTC27 NM_017735.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• Publications: 12 publications found

Genes affected

TTC27 (HGNC:25986): (tetratricopeptide repeat domain 27)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017735.5. 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
	TTC27	NM_017735.5	MANE Select	c.537+44G>C		intron	N/A	NP_060205.3
	TTC27	NM_001193509.2		c.387+44G>C		intron	N/A	NP_001180438.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC27	ENST00000317907.9	TSL:1 MANE Select	c.537+44G>C		intron	N/A	ENSP00000313953.4
	TTC27	ENST00000454690.1	TSL:3	n.88+12074G>C		intron	N/A	ENSP00000392883.1
	TTC27	ENST00000647819.1		n.537+44G>C		intron	N/A	ENSP00000497009.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20639 AN: 151936 Hom.: 1612 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.125

GnomAD2 exomes AF: 0.173 AC: 41598 AN: 240546 AF XY: 0.181

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.0974

Gnomad EAS exome AF: 0.306

Gnomad FIN exome AF: 0.157

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.152

GnomAD4 exome AF: 0.139 AC: 200085 AN: 1440050 Hom.: 16605 Cov.: 27 AF XY: 0.145 AC XY: 103950 AN XY: 716314

African (AFR) AF: 0.118 AC: 3910 AN: 33106

American (AMR) AF: 0.153 AC: 6677 AN: 43544

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 2476 AN: 25648

East Asian (EAS) AF: 0.278 AC: 10963 AN: 39478

South Asian (SAS) AF: 0.335 AC: 28204 AN: 84106

European-Finnish (FIN) AF: 0.152 AC: 7553 AN: 49694

Middle Eastern (MID) AF: 0.116 AC: 661 AN: 5702

European-Non Finnish (NFE) AF: 0.119 AC: 131055 AN: 1099090

Other (OTH) AF: 0.144 AC: 8586 AN: 59682

GnomAD4 genome AF: 0.136 AC: 20660 AN: 152054 Hom.: 1615 Cov.: 32 AF XY: 0.140 AC XY: 10410 AN XY: 74334

African (AFR) AF: 0.118 AC: 4877 AN: 41488

American (AMR) AF: 0.126 AC: 1919 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 334 AN: 3462

East Asian (EAS) AF: 0.295 AC: 1527 AN: 5174

South Asian (SAS) AF: 0.343 AC: 1647 AN: 4798

European-Finnish (FIN) AF: 0.158 AC: 1662 AN: 10550

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8330 AN: 67988

Other (OTH) AF: 0.128 AC: 270 AN: 2116

Alfa AF: 0.132 Hom.: 937

Bravo AF: 0.131

Asia WGS AF: 0.333 AC: 1155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.3
DANN	Benign	0.70
PhyloP100		0.057
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1031261; hg19: chr2-32865521; COSMIC: COSV58648669; COSMIC: COSV58648669;