NM_001164399.2:c.2267G>A

Variant names:

• chr14-59510684-C-T
• rs371749983
• NM_001164399.2:c.2267G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001164399.2(CCDC175):​c.2267G>A​(p.Arg756His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,537,196 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (1 hom.)
• Consequence: CCDC175 NM_001164399.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.19
• Publications: 1 publications found

Genes affected

CCDC175 (HGNC:19847): (coiled-coil domain containing 175)

ENSG00000258782 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.043376416).
• BP6: Variant 14-59510684-C-T is Benign according to our data. Variant chr14-59510684-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2390763.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC175	NM_001164399.2	c.2267G>A	p.Arg756His	missense_variant	Exon 19 of 20	ENST00000537690.7	NP_001157871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC175	ENST00000537690.7	c.2267G>A	p.Arg756His	missense_variant	Exon 19 of 20	5	NM_001164399.2	ENSP00000453940.1
CCDC175	ENST00000281581.5	c.2267G>A	p.Arg756His	missense_variant	Exon 19 of 20	5		ENSP00000452964.1
CCDC175	ENST00000553317.1	n.30G>A		non_coding_transcript_exon_variant	Exon 1 of 3	3
ENSG00000258782	ENST00000554253.1	n.428G>A		non_coding_transcript_exon_variant	Exon 4 of 6	5

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000898 AC: 13 AN: 144720 AF XY: 0.0000907

Gnomad AFR exome AF: 0.000262

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000941

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000191 AC: 264 AN: 1384912 Hom.: 1 Cov.: 31 AF XY: 0.000183 AC XY: 125 AN XY: 683364

African (AFR) AF: 0.0000950 AC: 3 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35722

South Asian (SAS) AF: 0.0000505 AC: 4 AN: 79234

European-Finnish (FIN) AF: 0.0000856 AC: 3 AN: 35030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.000226 AC: 244 AN: 1078844

Other (OTH) AF: 0.000155 AC: 9 AN: 57918

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152284 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74458

African (AFR) AF: 0.000192 AC: 8 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000110

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Apr 12, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.023
DANN	Benign	0.60
DEOGEN2	Benign	0.0034	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.043	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.11	N;.
PhyloP100		-3.2
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.41	N;N
Sift	Benign	0.48	T;T
Sift4G	Benign	0.52	T;T
Vest4		0.036
MVP		0.030
ClinPred		0.020	T
GERP RS		-4.6
Varity_R		0.017
gMVP		0.080
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs371749983; hg19: chr14-59977402;